Nanomedicine – Wikipedia

Medical application of nanotechnology

Nanomedicine is the medical application of nanotechnology.[1] Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials (materials whose structure is on the scale of nanometers, i.e. billionths of a meter).[2][3]

Functionalities can be added to nanomaterials by interfacing them with biological molecules or structures. The size of nanomaterials is similar to that of most biological molecules and structures; therefore, nanomaterials can be useful for both in vivo and in vitro biomedical research and applications. Thus far, the integration of nanomaterials with biology has led to the development of diagnostic devices, contrast agents, analytical tools, physical therapy applications, and drug delivery vehicles.

Nanomedicine seeks to deliver a valuable set of research tools and clinically useful devices in the near future.[4][5] The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that may include advanced drug delivery systems, new therapies, and in vivo imaging.[6] Nanomedicine research is receiving funding from the US National Institutes of Health Common Fund program, supporting four nanomedicine development centers.[7]

Nanomedicine sales reached $16 billion in 2015, with a minimum of $3.8 billion in nanotechnology R&D being invested every year. Global funding for emerging nanotechnology increased by 45% per year in recent years, with product sales exceeding $1 trillion in 2013.[8] As the nanomedicine industry continues to grow, it is expected to have a significant impact on the economy.

Nanotechnology has provided the possibility of delivering drugs to specific cells using the nanoparticles.[9][10] The overall drug consumption and side-effects may be lowered significantly by depositing the active pharmaceutical agent in the morbid region only and in no higher dose than needed. Targeted drug delivery is intended to reduce the side effects of drugs with concomitant decreases in consumption and treatment expenses. Additionally, targeted drug drug delivery reduces the side effect possessed by crude drug via minimizing undesired exposure to the healthy cells. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. This can potentially be achieved by molecular targeting by nanoengineered devices.[11][12] A benefit of using nanoscale for medical technologies is that smaller devices are less invasive and can possibly be implanted inside the body, plus biochemical reaction times are much shorter. These devices are faster and more sensitive than typical drug delivery.[13] The efficacy of drug delivery through nanomedicine is largely based upon: a) efficient encapsulation of the drugs, b) successful delivery of drug to the targeted region of the body, and c) successful release of the drug.[14] Several nano-delivery drugs were on the market by 2019.[15]

Drug delivery systems, lipid-[16] or polymer-based nanoparticles, can be designed to improve the pharmacokinetics and biodistribution of the drug.[17][18][19] However, the pharmacokinetics and pharmacodynamics of nanomedicine is highly variable among different patients.[20] When designed to avoid the body's defence mechanisms,[21] nanoparticles have beneficial properties that can be used to improve drug delivery. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell membranes and into cell cytoplasm. Triggered response is one way for drug molecules to be used more efficiently. Drugs are placed in the body and only activate on encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug delivery system where both hydrophilic and hydrophobic environments exist, improving the solubility.[22] Drug delivery systems may also be able to prevent tissue damage through regulated drug release; reduce drug clearance rates; or lower the volume of distribution and reduce the effect on non-target tissue. However, the biodistribution of these nanoparticles is still imperfect due to the complex host's reactions to nano- and microsized materials[21] and the difficulty in targeting specific organs in the body. Nevertheless, a lot of work is still ongoing to optimize and better understand the potential and limitations of nanoparticulate systems. While advancement of research proves that targeting and distribution can be augmented by nanoparticles, the dangers of nanotoxicity become an important next step in further understanding of their medical uses.[23] The toxicity of nanoparticles varies, depending on size, shape, and material. These factors also affect the build-up and organ damage that may occur. Nanoparticles are made to be long-lasting, but this causes them to be trapped within organs, specifically the liver and spleen, as they cannot be broken down or excreted. This build-up of non-biodegradable material has been observed to cause organ damage and inflammation in mice.[24] Magnetic targeted delivery of magnetic nanoparticles to the tumor site under the influence of inhomogeneous stationary magnetic fields may lead to enhanced tumor growth. In order to circumvent the pro-tumorigenic effects, alternating electromagnetic fields should be used.[25]

Nanoparticles are under research for their potential to decrease antibiotic resistance or for various antimicrobial uses.[26][27][28][29] Nanoparticles might also be used to circumvent multidrug resistance (MDR) mechanisms.[9]

Advances in lipid nanotechnology were instrumental in engineering medical nanodevices and novel drug delivery systems, as well as in developing sensing applications.[30] Another system for microRNA delivery under preliminary research is nanoparticles formed by the self-assembly of two different microRNAs deregulated in cancer.[31] One potential application is based on small electromechanical systems, such as nanoelectromechanical systems being investigated for the active release of drugs and sensors for possible cancer treatment with iron nanoparticles or gold shells.[32]

Some nanotechnology-based drugs that are commercially available or in human clinical trials include:

In vivo imaging is another area where tools and devices are being developed.[39] Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. In cardiovascular imaging, nanoparticles have potential to aid visualization of blood pooling, ischemia, angiogenesis, atherosclerosis, and focal areas where inflammation is present.[39]

The small size of nanoparticles endows them with properties that can be very useful in oncology, particularly in imaging.[9] Quantum dots (nanoparticles with quantum confinement properties, such as size-tunable light emission), when used in conjunction with MRI (magnetic resonance imaging), can produce exceptional images of tumor sites. Nanoparticles of cadmium selenide (quantum dots) glow when exposed to ultraviolet light. When injected, they seep into cancer tumors. The surgeon can see the glowing tumor, and use it as a guide for more accurate tumor removal. These nanoparticles are much brighter than organic dyes and only need one light source for excitation. This means that the use of fluorescent quantum dots could produce a higher contrast image and at a lower cost than today's organic dyes used as contrast media. The downside, however, is that quantum dots are usually made of quite toxic elements, but this concern may be addressed by use of fluorescent dopants.[40]

Tracking movement can help determine how well drugs are being distributed or how substances are metabolized. It is difficult to track a small group of cells throughout the body, so scientists used to dye the cells. These dyes needed to be excited by light of a certain wavelength in order for them to light up. While different color dyes absorb different frequencies of light, there was a need for as many light sources as cells. A way around this problem is with luminescent tags. These tags are quantum dots attached to proteins that penetrate cell membranes.[40] The dots can be random in size, can be made of bio-inert material, and they demonstrate the nanoscale property that color is size-dependent. As a result, sizes are selected so that the frequency of light used to make a group of quantum dots fluoresce is an even multiple of the frequency required to make another group incandesce. Then both groups can be lit with a single light source. They have also found a way to insert nanoparticles[41] into the affected parts of the body so that those parts of the body will glow showing the tumor growth or shrinkage or also organ trouble.[42]

Nanotechnology-on-a-chip is one more dimension of lab-on-a-chip technology. Magnetic nanoparticles, bound to a suitable antibody, are used to label specific molecules, structures or microorganisms. In particular silica nanoparticles are inert from the photophysical point of view and might accumulate a large number of dye(s) within the nanoparticle shell.[43] Gold nanoparticles tagged with short segments of DNA can be used for detection of genetic sequence in a sample. Multicolor optical coding for biological assays has been achieved by embedding different-sized quantum dots into polymeric microbeads. Nanopore technology for analysis of nucleic acids converts strings of nucleotides directly into electronic signatures.[citation needed]

Sensor test chips containing thousands of nanowires, able to detect proteins and other biomarkers left behind by cancer cells, could enable the detection and diagnosis of cancer in the early stages from a few drops of a patient's blood.[44] Nanotechnology is helping to advance the use of arthroscopes, which are pencil-sized devices that are used in surgeries with lights and cameras so surgeons can do the surgeries with smaller incisions. The smaller the incisions the faster the healing time which is better for the patients. It is also helping to find a way to make an arthroscope smaller than a strand of hair.[45]

Research on nanoelectronics-based cancer diagnostics could lead to tests that can be done in pharmacies. The results promise to be highly accurate and the product promises to be inexpensive. They could take a very small amount of blood and detect cancer anywhere in the body in about five minutes, with a sensitivity that is a thousand times better a conventional laboratory test. These devices are built with nanowires to detect cancer proteins; each nanowire detector is primed to be sensitive to a different cancer marker.[32] The biggest advantage of the nanowire detectors is that they could test for anywhere from ten to one hundred similar medical conditions without adding cost to the testing device.[46] Nanotechnology has also helped to personalize oncology for the detection, diagnosis, and treatment of cancer. It is now able to be tailored to each individual's tumor for better performance. They have found ways that they will be able to target a specific part of the body that is being affected by cancer.[47]

In contrast to dialysis, which works on the principle of the size related diffusion of solutes and ultrafiltration of fluid across a semi-permeable membrane, the purification with nanoparticles allows specific targeting of substances.[48] Additionally larger compounds which are commonly not dialyzable can be removed.[49]

The purification process is based on functionalized iron oxide or carbon coated metal nanoparticles with ferromagnetic or superparamagnetic properties.[50] Binding agents such as proteins,[48] antibiotics,[51] or synthetic ligands[52] are covalently linked to the particle surface. These binding agents are able to interact with target species forming an agglomerate. Applying an external magnetic field gradient allows exerting a force on the nanoparticles. Hence the particles can be separated from the bulk fluid, thereby cleaning it from the contaminants.[53][54]

The small size (< 100nm) and large surface area of functionalized nanomagnets leads to advantageous properties compared to hemoperfusion, which is a clinically used technique for the purification of blood and is based on surface adsorption. These advantages are high loading and accessible for binding agents, high selectivity towards the target compound, fast diffusion, small hydrodynamic resistance, and low dosage.[55]

Nanotechnology may be used as part of tissue engineering to help reproduce or repair or reshape damaged tissue using suitable nanomaterial-based scaffolds and growth factors. Tissue engineering if successful may replace conventional treatments like organ transplants or artificial implants. Nanoparticles such as graphene, carbon nanotubes, molybdenum disulfide and tungsten disulfide are being used as reinforcing agents to fabricate mechanically strong biodegradable polymeric nanocomposites for bone tissue engineering applications. The addition of these nanoparticles in the polymer matrix at low concentrations (~0.2 weight%) leads to significant improvements in the compressive and flexural mechanical properties of polymeric nanocomposites.[56][57] Potentially, these nanocomposites may be used as a novel, mechanically strong, light weight composite as bone implants.[citation needed]

For example, a flesh welder was demonstrated to fuse two pieces of chicken meat into a single piece using a suspension of gold-coated nanoshells activated by an infrared laser. This could be used to weld arteries during surgery.[58]Another example is nanonephrology, the use of nanomedicine on the kidney.

Neuro-electronic interfacing is a visionary goal dealing with the construction of nanodevices that will permit computers to be joined and linked to the nervous system. This idea requires the building of a molecular structure that will permit control and detection of nerve impulses by an external computer. A refuelable strategy implies energy is refilled continuously or periodically with external sonic, chemical, tethered, magnetic, or biological electrical sources, while a non-refuelable strategy implies that all power is drawn from internal energy storage which would stop when all energy is drained. A nanoscale enzymatic biofuel cell for self-powered nanodevices have been developed that uses glucose from biofluids including human blood and watermelons.[59] One limitation to this innovation is the fact that electrical interference or leakage or overheating from power consumption is possible. The wiring of the structure is extremely difficult because they must be positioned precisely in the nervous system. The structures that will provide the interface must also be compatible with the body's immune system.[60]

Molecular nanotechnology is a speculative subfield of nanotechnology regarding the possibility of engineering molecular assemblers, machines which could re-order matter at a molecular or atomic scale.[citation needed] Nanomedicine would make use of these nanorobots, introduced into the body, to repair or detect damages and infections. Molecular nanotechnology is highly theoretical, seeking to anticipate what inventions nanotechnology might yield and to propose an agenda for future inquiry. The proposed elements of molecular nanotechnology, such as molecular assemblers and nanorobots are far beyond current capabilities.[1][60][61] Future advances in nanomedicine could give rise to life extension through the repair of many processes thought to be responsible for aging. K. Eric Drexler, one of the founders of nanotechnology, postulated cell repair machines, including ones operating within cells and utilizing as yet hypothetical molecular machines, in his 1986 book Engines of Creation, with the first technical discussion of medical nanorobots by Robert Freitas appearing in 1999.[1] Raymond Kurzweil, a futurist and transhumanist, stated in his book The Singularity Is Near that he believes that advanced medical nanorobotics could completely remedy the effects of aging by 2030.[62] According to Richard Feynman, it was his former graduate student and collaborator Albert Hibbs who originally suggested to him (c.1959) the idea of a medical use for Feynman's theoretical micromachines (see nanotechnology). Hibbs suggested that certain repair machines might one day be reduced in size to the point that it would, in theory, be possible to (as Feynman put it) "swallow the doctor". The idea was incorporated into Feynman's 1959 essay There's Plenty of Room at the Bottom.[63]

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Nanomedicine - Wikipedia

Nanotechnology Timeline | National Nanotechnology Initiative

This timeline features Premodern example of nanotechnology, as well as Modern Era discoveries and milestones in the field of nanotechnology.

Early examples of nanostructured materials were based on craftsmens empirical understanding and manipulation of materials. Use of high heat was one common step in their processes to produce these materials with novel properties.

The Lycurgus Cup at the British Museum, lit from the outside (left) and from the inside (right)

4th Century: The Lycurgus Cup (Rome) is an example of dichroic glass; colloidal gold and silver in the glass allow it to look opaque green when lit from outside but translucent red when light shines through the inside. (Images at left.)

9th-17th Centuries: Glowing, glittering luster ceramic glazes used in the Islamic world, and later in Europe, contained silver or copper or other metallic nanoparticles. (Image at right.)

6th-15th Centuries: Vibrant stained glass windows in European cathedrals owed their rich colors to nanoparticles of gold chloride and other metal oxides and chlorides; gold nanoparticles also acted as photocatalytic air purifiers. (Image at left.)

13th-18th Centuries: Damascus saber blades contained carbon nanotubes and cementite nanowiresan ultrahigh-carbon steel formulation that gave them strength, resilience, the ability to hold a keen edge, and a visible moir pattern in the steel that give the blades their name. (Images below.)

These are based on increasingly sophisticated scientific understanding and instrumentation, as well as experimentation.

1857: Michael Faraday discovered colloidal ruby gold, demonstrating that nanostructured gold under certain lighting conditions produces different-colored solutions.

1936: Erwin Mller, working at Siemens Research Laboratory, invented the field emission microscope, allowing near-atomic-resolution images of materials.

1947: John Bardeen, William Shockley, and Walter Brattain at Bell Labs discovered the semiconductor transistor and greatly expanded scientific knowledge of semiconductor interfaces, laying the foundation for electronic devices and the Information Age.

1950: Victor La Mer and Robert Dinegar developed the theory and a process for growing monodisperse colloidal materials. Controlled ability to fabricate colloids enables myriad industrial uses such as specialized papers, paints, and thin films, even dialysis treatments.

1951: Erwin Mller pioneered the field ion microscope, a means to image the arrangement of atoms at the surface of a sharp metal tip; he first imaged tungsten atoms.

1956: Arthur von Hippel at MIT introduced many concepts ofand coined the termmolecular engineering as applied to dielectrics, ferroelectrics, and piezoelectrics

1958: Jack Kilby of Texas Instruments originated the concept of, designed, and built the first integrated circuit, for which he received the Nobel Prize in 2000. (Image at left.)

1959: Richard Feynman of the California Institute of Technology gave what is considered to be the first lecture on technology and engineering at the atomic scale, "There's Plenty of Room at the Bottom" at an American Physical Society meeting at Caltech. (Image at right.)

1965: Intel co-founder Gordon Moore described in Electronics magazine several trends he foresaw in the field of electronics. One trend now known as Moores Law, described the density of transistors on an integrated chip (IC) doubling every 12 months (later amended to every 2 years). Moore also saw chip sizes and costs shrinking with their growing functionalitywith a transformational effect on the ways people live and work. That the basic trend Moore envisioned has continued for 50 years is to a large extent due to the semiconductor industrys increasing reliance on nanotechnology as ICs and transistors have approached atomic dimensions.1974: Tokyo Science University Professor Norio Taniguchi coined the term nanotechnology to describe precision machining of materials to within atomic-scale dimensional tolerances. (See graph at left.)

1981: Gerd Binnig and Heinrich Rohrer at IBMs Zurich lab invented the scanning tunneling microscope, allowing scientists to "see" (create direct spatial images of) individual atoms for the first time. Binnig and Rohrer won the Nobel Prize for this discovery in 1986.

1981: Russias Alexei Ekimov discovered nanocrystalline, semiconducting quantum dots in a glass matrix and conducted pioneering studies of their electronic and optical properties.

1985: Rice University researchers Harold Kroto, Sean OBrien, Robert Curl, and Richard Smalley discovered the Buckminsterfullerene (C60), more commonly known as the buckyball, which is a molecule resembling a soccer ball in shape and composed entirely of carbon, as are graphite and diamond. The team was awarded the 1996 Nobel Prize in Chemistry for their roles in this discovery and that of the fullerene class of molecules more generally. (Artist's rendering at right.)

1985: Bell Labss Louis Brus discovered colloidal semiconductor nanocrystals (quantum dots), for which he shared the 2008 Kavli Prize in Nanotechnology.

1986: Gerd Binnig, Calvin Quate, and Christoph Gerber invented the atomic force microscope, which has the capability to view, measure, and manipulate materials down to fractions of a nanometer in size, including measurement of various forces intrinsic to nanomaterials.

1989:Don Eigler and Erhard Schweizer at IBM's Almaden Research Center manipulated 35 individual xenon atoms to spell out the IBM logo. This demonstration of the ability to precisely manipulate atoms ushered in the applied use of nanotechnology. (Image at left.)

1990s: Early nanotechnology companies began to operate, e.g., Nanophase Technologies in 1989, Helix Energy Solutions Group in 1990, Zyvex in 1997, Nano-Tex in 1998.

1991: Sumio Iijima of NEC is credited with discovering the carbon nanotube (CNT), although there were early observations of tubular carbon structures by others as well. Iijima shared the Kavli Prize in Nanoscience in 2008 for this advance and other advances in the field. CNTs, like buckyballs, are entirely composed of carbon, but in a tubular shape. They exhibit extraordinary properties in terms of strength, electrical and thermal conductivity, among others. (Image below.)

1992: C.T. Kresge and colleagues at Mobil Oil discovered the nanostructured catalytic materials MCM-41 and MCM-48, now used heavily in refining crude oil as well as for drug delivery, water treatment, and other varied applications.

1993: Moungi Bawendi of MIT invented a method for controlled synthesis of nanocrystals (quantum dots), paving the way for applications ranging from computing to biology to high-efficiency photovoltaics and lighting. Within the next several years, work by other researchers such as Louis Brus and Chris Murray also contributed methods for synthesizing quantum dots.

1998: The Interagency Working Group on Nanotechnology (IWGN) was formed under the National Science and Technology Council to investigate the state of the art in nanoscale science and technology and to forecast possible future developments. The IWGNs study and report, Nanotechnology Research Directions: Vision for the Next Decade (1999) defined the vision for and led directly to formation of the U.S. National Nanotechnology Initiative in 2000.

1999: Cornell University researchers Wilson Ho and Hyojune Lee probed secrets of chemical bonding by assembling a molecule [iron carbonyl Fe(CO)2] from constituent components [iron (Fe) and carbon monoxide (CO)] with a scanning tunneling microscope. (Image at left.)

1999: Chad Mirkin at Northwestern University invented dip-pen nanolithography (DPN), leading to manufacturable, reproducible writing of electronic circuits as well as patterning of biomaterials for cell biology research, nanoencryption, and other applications. (Image below right.)

1999early 2000s: Consumer products making use of nanotechnology began appearing in the marketplace, including lightweight nanotechnology-enabled automobile bumpers that resist denting and scratching, golf balls that fly straighter, tennis rackets that are stiffer (therefore, the ball rebounds faster), baseball bats with better flex and "kick," nano-silver antibacterial socks, clear sunscreens, wrinkle- and stain-resistant clothing, deep-penetrating therapeutic cosmetics, scratch-resistant glass coatings, faster-recharging batteries for cordless electric tools, and improved displays for televisions, cell phones, and digital cameras.

2000: President Clinton launched the National Nanotechnology Initiative (NNI) to coordinate Federal R&D efforts and promote U.S. competitiveness in nanotechnology. Congress funded the NNI for the first time in FY2001. The NSET Subcommittee of the NSTC was designated as the interagency group responsible for coordinating the NNI.

2003: Congress enacted the 21st Century Nanotechnology Research and Development Act (P.L. 108-153). The act provided a statutory foundation for the NNI, established programs, assigned agency responsibilities, authorized funding levels, and promoted research to address key issues.

2003: Naomi Halas, Jennifer West, Rebekah Drezek, and Renata Pasqualin at Rice University developed gold nanoshells, which when tuned in size to absorb near-infrared light, serve as a platform for the integrated discovery, diagnosis, and treatment of breast cancer without invasive biopsies, surgery, or systemically destructive radiation or chemotherapy.2004: The European Commission adopted the Communication Towards a European Strategy for Nanotechnology, COM(2004) 338, which proposed institutionalizing European nanoscience and nanotechnology R&D efforts within an integrated and responsible strategy, and which spurred European action plans and ongoing funding for nanotechnology R&D. (Image at left.)

2004: Britains Royal Society and the Royal Academy of Engineering published Nanoscience and Nanotechnologies: Opportunities and Uncertainties advocating the need to address potential health, environmental, social, ethical, and regulatory issues associated with nanotechnology.

2004: SUNY Albany launched the first college-level education program in nanotechnology in the United States, the College of Nanoscale Science and Engineering.

2005: Erik Winfree and Paul Rothemund from the California Institute of Technology developed theories for DNA-based computation and algorithmic self-assembly in which computations are embedded in the process of nanocrystal growth.

2006: James Tour and colleagues at Rice University built a nanoscale car made of oligo(phenylene ethynylene) with alkynyl axles and four spherical C60 fullerene (buckyball) wheels. In response to increases in temperature, the nanocar moved about on a gold surface as a result of the buckyball wheels turning, as in a conventional car. At temperatures above 300C it moved around too fast for the chemists to keep track of it! (Image at left.)

2007: Angela Belcher and colleagues at MIT built a lithium-ion battery with a common type of virus that is nonharmful to humans, using a low-cost and environmentally benign process. The batteries have the same energy capacity and power performance as state-of-the-art rechargeable batteries being considered to power plug-in hybrid cars, and they could also be used to power personal electronic devices. (Image at right.)

2008: The first official NNI Strategy for Nanotechnology-Related Environmental, Health, and Safety (EHS) Research was published, based on a two-year process of NNI-sponsored investigations and public dialogs. This strategy document was updated in 2011, following a series of workshops and public review.

20092010: Nadrian Seeman and colleagues at New York University createdseveral DNA-like robotic nanoscale assembly devices.One is a process for creating 3D DNA structures using synthetic sequences of DNA crystals that can be programmed to self-assemble using sticky ends and placement in a set order and orientation.Nanoelectronics could benefit:the flexibility and density that 3D nanoscale components allow could enable assembly of parts that are smaller, more complex, and more closely spaced. Another Seeman creation (with colleagues at Chinas Nanjing University) is a DNA assembly line. For this work, Seeman shared the Kavli Prize in Nanoscience in 2010.

2010: IBM used a silicon tip measuring only a few nanometers at its apex (similar to the tips used in atomic force microscopes) to chisel away material from a substrate to create a complete nanoscale 3D relief map of the world one-one-thousandth the size of a grain of saltin 2 minutes and 23 seconds. This activity demonstrated a powerful patterning methodology for generating nanoscale patterns and structures as small as 15 nanometers at greatly reduced cost and complexity, opening up new prospects for fields such as electronics, optoelectronics, and medicine. (Image below.)

2011:The NSET Subcommittee updated both the NNI Strategic Plan and the NNI Environmental, Health, and Safety Research Strategy, drawing on extensive input from public workshops and online dialog with stakeholders from Government, academia, NGOs, and the public, and others.

2012: The NNI launched two more Nanotechnology Signature Initiatives (NSIs)--Nanosensors and the Nanotechnology Knowledge Infrastructure (NKI)--bringing the total to five NSIs.

2013: -The NNI starts the next round of Strategic Planning, starting with the Stakeholder Workshop. -Stanford researchers develop the first carbon nanotube computer.

2014: -The NNI releases the updated 2014 Strategic Plan. -The NNI releases the 2014 Progress Review on the Coordinated Implementation of the NNI 2011 Environmental, Health, and Safety Research Strategy.

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Nanotechnology Timeline | National Nanotechnology Initiative

Nano Medicine: Meaning, Advantages and Disadvantages – BioTechnology Notes

In this article we will discuss about Nano Medicine:- 1. Meaning of Nano Medicine 2. Advantages of Nano Medicine 3. Disadvantages.

The application of nanotechnology in medicine is often referred to as Nano medicine. Nano medicine is the preservation and improvement of human health using molecular tools and molecular knowledge of the human body. It covers areas such as nanoparticle drug delivery and possible future applications of molecular nanotechnology (MNT) and Nano-vaccinology.

The human body is comprised of molecules. Hence, the availability of molecular nanotechnology will permit dramatic progress in human medical services. More than just an extension of molecular medicine, Nano medicine will help us understand how the biological machinery inside living cells operates at the Nano scale so that it can be employed in molecular machine systems to address complicated medical conditions such as cancer, AIDS, ageing and thereby bring about significant improvement and extension of natural human biological structure and function at the molecular scale.

Nano medical approaches to drug delivery centre on developing Nano scale particles or molecules to improve drug bioavailability that refers to the presence of drug molecules in the body part where they are actually needed and will probably do the most good. It is all about targeting the molecules and delivering drugs with cell precision.

The use of Nano robots in medicine would totally change the world of medicine once it is realized. For instance, by introducing these Nano robots into the body damages and infections can be detected and repaired. In short it holds that capability to change the traditional approach of treating diseases and naturally occurring conditions in the human beings.

1. Advanced therapies with reduced degree of invasiveness.

2. Reduced negative effects of drugs and surgical procedures.

3. Faster, smaller and highly sensitive diagnostic tools.

4. Cost effectiveness of medicines and disease management procedures as a whole.

5. Unsolved medical problems such as cancer, benefiting from the Nano medical approach.

6. Reduced mortality and morbidity rates and increased longevity in return.

1. Lack of proper knowledge about the effect of nanoparticles on biochemical pathways and processes of human body.

2. Scientists are primarily concerned about the toxicity, characterization and exposure pathways associated with Nano medicine that might pose a serious threat to the human beings and environment.

3. The societys ethical use of Nano medicine beyond the concerned safety issues, poses a serious question to the researchers.

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Nano Medicine: Meaning, Advantages and Disadvantages - BioTechnology Notes

Air New Zealand Limited (NZSE:AIR) insiders have profited after buying stock worth NZ$3.8m last year, current gains stand at NZ$737k – Simply Wall St

Air New Zealand Limited (NZSE:AIR) insiders have profited after buying stock worth NZ$3.8m last year, current gains stand at NZ$737k  Simply Wall St

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Air New Zealand Limited (NZSE:AIR) insiders have profited after buying stock worth NZ$3.8m last year, current gains stand at NZ$737k - Simply Wall St

The Skeptics Guide to the Future: What Yesterdays Science and Science Fiction Tell Us About the World of Tomorrow – Next Big Idea Club Magazine

The Skeptics Guide to the Future: What Yesterdays Science and Science Fiction Tell Us About the World of Tomorrow  Next Big Idea Club Magazine

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The Skeptics Guide to the Future: What Yesterdays Science and Science Fiction Tell Us About the World of Tomorrow - Next Big Idea Club Magazine

Incredible Creatures that Use Photosynthesis For Energy – Futurism

You have probably heard about a trend called breatharianism, a 'diet' claiming that humans can sustain themselves without food and water, surviving on only light and air. This is a potentially lethal practice and several practitioners have, quite obviously, died because of it. Animals and humans are heterotrophic organisms, unable to produce their own food, thus they depend on organic sources to provide it.

Plants, on the other hand, are autotrophic organismsthat are able to produce food out of inorganic matter. With photosynthesis, they convert water, minerals and sunlight into glucose and oxygen. Plants use glucose as their source of energy needed for growth and life. Their role in the life cycle is important, because they serve as a source of food and oxygen for other living organisms.

But nature never fails to surprise us, sometimes ''the laws'' can be broken. Scientists have found some animals that can, just like plants, survive on photosynthesis:

Sea Slug(Elysia chlorotica) is an extraordinarily beautiful slug living in the waters of the east coast of the United States and Canada. It's distinctive feature is green colored, leaf-shaped body. The slug eats algae (Vaucheria litorea), but it's not it's only source of energy!

It seems like this slug stole photosynthetic organelles (chloroplasts) and some genes from the algae, which enables them to live without eating! They can spend their days laying out in the sun and, just like plants and green algae, get their energy through photosynthesis. The symbiosis that enables algae's chloroplasts to work for slug is called kleptoplasty.

Pea Aphid (Acyrthospihon pisum) is an insect living worldwide that feeds on plants (legumes). Even though they may look like any other insect, unpleasant or even terrifying to some, they truly are amazing.

Pea Aphids are capable of producing carotenoids, pigments found in chloroplasts (photosynthetic organelles) and chromoplasts, giving them orange-reddish colour and helping chlorophyll with photosynthesis. In aphids, carotenoids are responsible for their colour, some of them don't have it and are white. It also seems like carotenoids serve not only as a beauty compound, but they can also be usedto convert sunlight into energy. However, these correlations are not yet clear and well researched.

Spotted Salamander (Ambystoma maculatum), just like the sea slug, it lives in symbiotic relationship with algae. They were found in embryos of the animal. The salamander's embryos are found in clear colored eggs, laid by the females on the underwater plants, close to the surface, so that the light can reach them.

It seems like green algae help embryos get much-needed energy for growth and development from sunlight, whileproviding anextra source of energy(this, in turn,increases theirchances ofsurvival). Spotted Salamanders are the highest developed animal species and the only ones among all vertebrae, that can directly benefit from photosynthesis. Usually, the immune system of highly developed organisms will prevent such symbiotic behavior.

These special animals just show how complex the living world is, and that the line between plants and animals may not be so well-defined. It makes us wonder where evolution will take us in the next few billions of years (if we last that long) Maybe one day, even humans could benefit from photosynthesis. Just imagine the possibilities that this kind of life opens.

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Examples of Victimless Crimes | LawInfo

Last updated May 12, 2021

Is there such a thing as a victimless crime? Yes. Criminal justice laws are created by the government to restrict unwanted behavior and actions. Many of these criminal laws are meant to protect others, such as laws against assault or abuse. However, a number of laws criminalize consensual behavior or actions where there are no victims. This may include laws against recreational drug use or prostitution.

Unfortunately, the courts and judges do not always take into account whether a crime is victimless when enforcing laws. However, your criminal defense attorney may be able to negotiate a reduced sentence or lesser penalties by showing the court that there was no identifiable victim. Talk to an experienced criminal defense lawyer for legal advice in your case.

A victimless crime is generally an illegal criminal act that does not have an identifiable victim. This generally includes actions that only involve the perpetrator or something voluntary between consenting adults. Victimless crimes are also known as crimes against the state that do not harm society.

The police may claim that there is no such thing as a victimless crime, but is that really true? There are laws in other countries that prohibit criticism of the government, which criminalizes free speech. Other countries criminalize consensual behavior like same-sex relationships or drinking alcohol. Many of the laws that criminalize harmless behavior are based on opinions about morality.

There is no set definition of a victimless crime, and each person may have a different opinion about whether a criminal offense is actually victimless. Some of the common examples of actions that may be called victimless crimes include:

There is often a fine line between what is considered a crime or not. For example, going to Las Vegas and playing poker for money is legal. However, playing a poker game for money in another state may be illegal gambling. Smoking recreational marijuana is legal in states like California andOregon, but doing the same thing in Alabama could get you thrown in jail. State criminal laws and regional attitudes can make a big difference in whether victimless activities are against the law or permissible.

Prostitution is legal in many countries. It's even legal in parts of Nevada. However, in the rest of the U.S.,solicitationof sexual acts in exchange for money is against the law. Criminalizing sex work does not eliminate the act but drives it underground. When treated as a crime, sex workers may be less willing to come forward to report more serious offenses, like violence or sexual assault.

There are many terminal diseases or debilitating conditions that leave patients suffering needlessly. For many of these people, suicide may be the best way to die with dignity. In states with assisted suicide laws, these people can make the decision to die on their own terms instead of continuing to suffer. However, in most states, suicide and assisted suicide is against the law. Prohibition of end-of-life care decisions can end up victimizing the person the laws are meant to protect.

The attitudes toward drug use are changing in the U.S. Not long ago, drugs like marijuana were illegal in all forms in all states. Now, a majority of states havemedical marijuanalaws, and a number of states are also legalizing marijuana for recreational use. More states are beginning to decriminalize drug possession, treating drug offenses as a substance abuse problem rather than a crime. Categorizing drugs as medically useful or harmful is not always based on science. However, in some states, the victimless crime of marijuana possession can still lead to a prison sentence.

Gambling is one of the most common criminal activities that people do not consider a crime. Betting on a March Madness bracket or Super Bowl pool at work may technically be against the law. A poker game between friends seems harmless, but it may violate state anti-gambling laws. However, state-sanctioned gambling may be totally legal, including the buying of lottery tickets. Many states have exceptions for charitable gaming or tribal casinos.

Homelessness is a major concern in many states. The simple response for many states is to criminalize the actions associated with homelessness instead of addressing the underlying issues. This includes laws against:

Homelessness may be the result of substance abuse, mental health conditions, domestic violence, or even an unexpected medical emergency. Criminalizing homelessness is a temporary measure that does not do anything to help those in need.

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Examples of Victimless Crimes | LawInfo

Gene therapy | Description, Uses, Examples, & Safety Issues

Summary

gene therapy, also called gene transfer therapy, introduction of a normal gene into an individuals genome in order to repair a mutation that causes a genetic disease. When a normal gene is inserted into the nucleus of a mutant cell, the gene most likely will integrate into a chromosomal site different from the defective allele; although that may repair the mutation, a new mutation may result if the normal gene integrates into another functional gene. If the normal gene replaces the mutant allele, there is a chance that the transformed cells will proliferate and produce enough normal gene product for the entire body to be restored to the undiseased phenotype.

Human gene therapy has been attempted on somatic (body) cells for diseases such as cystic fibrosis, adenosine deaminase deficiency, familial hypercholesterolemia, cancer, and severe combined immunodeficiency (SCID) syndrome. Somatic cells cured by gene therapy may reverse the symptoms of disease in the treated individual, but the modification is not passed on to the next generation. Germline gene therapy aims to place corrected cells inside the germ line (e.g., cells of the ovary or testis). If that is achieved, those cells will undergo meiosis and provide a normal gametic contribution to the next generation. Germline gene therapy has been achieved experimentally in animals but not in humans.

Scientists have also explored the possibility of combining gene therapy with stem cell therapy. In a preliminary test of that approach, scientists collected skin cells from a patient with alpha-1 antitrypsin deficiency (an inherited disorder associated with certain types of lung and liver disease), reprogrammed the cells into stem cells, corrected the causative gene mutation, and then stimulated the cells to mature into liver cells. The reprogrammed, genetically corrected cells functioned normally.

Prerequisites for gene therapy include finding the best delivery system (often a virus, typically referred to as a viral vector) for the gene, demonstrating that the transferred gene can express itself in the host cell, and establishing that the procedure is safe. Few clinical trials of gene therapy in humans have satisfied all those conditions, often because the delivery system fails to reach cells or the genes are not expressed by cells. Improved gene therapy systems are being developed by using nanotechnology. A promising application of that research involves packaging genes into nanoparticles that are targeted to cancer cells, thereby killing cancer cells specifically and leaving healthy cells unharmed.

Some aspects of gene therapy, including genetic manipulation and selection, research on embryonic tissue, and experimentation on human subjects, have aroused ethical controversy and safety concerns. Some objections to gene therapy are based on the view that humans should not play God and interfere in the natural order. On the other hand, others have argued that genetic engineering may be justified where it is consistent with the purposes of God as creator. Some critics are particularly concerned about the safety of germline gene therapy, because any harm caused by such treatment could be passed to successive generations. Benefits, however, would also be passed on indefinitely. There also has been concern that the use of somatic gene therapy may affect germ cells.

Although the successful use of somatic gene therapy has been reported, clinical trials have revealed risks. In 1999 American teenager Jesse Gelsinger died after having taken part in a gene therapy trial. In 2000 researchers in France announced that they had successfully used gene therapy to treat infants who suffered from X-linked SCID (XSCID; an inherited disorder that affects males). The researchers treated 11 patients, two of whom later developed a leukemia-like illness. Those outcomes highlight the difficulties foreseen in the use of viral vectors in somatic gene therapy. Although the viruses that are used as vectors are disabled so that they cannot replicate, patients may suffer an immune response.

Another concern associated with gene therapy is that it represents a form of eugenics, which aims to improve future generations through the selection of desired traits. While some have argued that gene therapy is eugenic, others claim that it is a treatment that can be adopted to avoid disability. To others, such a view of gene therapy legitimates the so-called medical model of disability (in which disability is seen as an individual problem to be fixed with medicine) and raises peoples hopes for new treatments that may never materialize.

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Gene therapy | Description, Uses, Examples, & Safety Issues

Gene therapy: The Potential for Treating Type 1 Diabetes – Healthline

Many people whove recently received a diagnosis of type 1 diabetes (T1D) immediately think, When will there be a cure?

While the potential for a cure has been dangling in front of people with T1D for what seems like forever, more researchers currently believe that gene therapy could finally one day soon, even be the so-called cure thats been so elusive.

This article will explain what gene therapy is, how its similar to gene editing, and how gene therapy could potentially be the cure for T1D, helping millions of people around the world.

Gene therapy is a medical field of study that focuses on the genetic modification of human cells to treat or sometimes even cure a particular disease. This happens by reconstructing or repairing defective or damaged genetic material in your body.

This advanced technology is only in the early research phases of clinical trials for treating diabetes in the United States. Yet, it has the potential to treat and cure a wide range of other conditions beyond just T1D, including AIDS, cancer, cystic fibrosis (a disorder that damages your lungs, digestive tract, and other organs), heart disease, and hemophilia (a disorder in which your blood has trouble clotting).

For T1D, gene therapy could look like the reprogramming of alternative cells, making those reprogrammed cells perform the functions your original insulin-producing beta cells would otherwise perform. If you have with diabetes, that includes producing insulin.

But the reprogrammed cells would be different enough from beta cells so that your own immune system wouldnt recognize them as new cells and attack them, which is what happens in the development of T1D.

While gene therapy is still in its infancy and available only in clinical trials, the evidence so far is becoming clearer about the potential benefits of this treatment.

In a 2018 study, researchers engineered alpha cells to function just like beta cells. They created an adeno-associated viral (AAV) vector to deliver two proteins, pancreatic and duodenal homeobox 1 and MAF basic leucine zipper transcription factor A, to a mouses pancreas. These two proteins help with beta cell proliferation, maturation, and function.

Alpha cells are the ideal type of cell to transform into beta-like cells because not only are they also located within the pancreas, but theyre abundant in your body and similar enough to beta cells that the transformation is possible. Beta cells produce insulin to lower your blood sugar levels while alpha cells produce glucagon, which increases your blood sugar levels.

In the study, mouse blood sugar levels were normal for 4 months with gene therapy, all without immunosuppressant drugs, which inhibit or prevent the activity of your immune system. The newly created alpha cells, performing just like beta cells, were resistant to the bodys immune attacks.

But the normal glucose levels observed in the mice werent permanent. This could potentially translate into several years of normal glucose levels in humans rather than a longtime cure.

In this Wisconsin study from 2013 (updated as of 2017), researchers found that when a small sequence of DNA was injected into the veins of rats with diabetes, it created insulin-producing cells that normalized blood glucose levels for up to 6 weeks. That was all from a single injection.

This is a landmark clinical trial, as it was the first research study to validate a DNA-based insulin gene therapy that could potentially one day treat T1D in humans.

This was how the study worked:

The researchers are now working on increasing the time interval between therapy DNA injections from 6 weeks to 6 months to provide more relief for people with T1D in the future.

While this is all very exciting, more research is needed to determine how practical the therapy is for people. Eventually, the hope is that the AAV vectors could eventually be delivered to the pancreas through a nonsurgical, endoscopic procedure, in which a doctor uses a medical device with a light attached to look inside your body.

These kinds of gene therapy wouldnt be a one-and-done cure. But it would provide a lot of relief to people with diabetes to perhaps enjoy several years of nondiabetes glucose numbers without taking insulin.

If subsequent trials in other nonhuman primates are successful, human trials may soon begin for the T1D treatment.

Does that count as a cure?

It all depends on who you ask because the definition of a cure for T1D varies.

Some people believe that a cure is a one-and-done endeavor. They see a cure as meaning youd never have to think about taking insulin, checking blood sugars, or the highs and lows of diabetes ever again. This even means you wouldnt have to ever go back to a hospital for a gene therapy follow-up treatment.

Other people think that a once-in-a-few-years treatment of gene editing may be enough of a therapy plan to count as a cure.

Many others believe that you need to fix the underlying autoimmune response to truly be cured, and some people dont really care one way or another, as long as their blood sugars are normal, and the mental tax of diabetes is relieved.

One potential one-and-done therapy could be gene editing, which is slightly different from gene therapy.

The idea behind gene editing is to reprogram your bodys DNA, and if you have type 1 diabetes, the idea is to get at the underlying cause of the autoimmune attack that destroyed your beta cells and caused T1D to begin with.

Two well-known companies, CRISPR Therapeutics and regenerative med-tech company ViaCyte, have been collaborating for a few years to use gene editing to create islet cells, encapsulate them, and then implant them into your body. These protected, transplanted islet cells would be safe from an immune system attack, which would otherwise be the typical response if you have T1D.

The focus of gene editing is to simply cut out the bad parts of our DNA in order to avoid conditions such as diabetes altogether and to stop the continuous immune response (beta cell attack) that people who already have diabetes experience daily (without their conscious awareness).

The gene editing done by CRISPR in their partnership with ViaCyte is creating insulin-producing islet cells that can evade an autoimmune response. These technology and research are ever evolving and hold a lot of promise.

Additionally, a 2017 study shows that a T1Dcure may one day be possible by using gene-editing technology.

Both gene therapy and gene editing hold a lot of promise for people living with T1D who are hoping for an eventual future without needing to take insulin or immunosuppressant therapy.

Gene therapy research continues, looking at how certain cells in the body could be reprogrammed to start making insulin and not experience an immune system response, such as those who develop T1D.

While gene therapy and gene-editing therapy are still in their early stages (and much has been held up by the coronavirus disease 19 [COVID-19] pandemic), theres a lot of hope for a T1D cure in our near future.

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Gene therapy: The Potential for Treating Type 1 Diabetes - Healthline

History of Gene Therapy | Discovery and Evolution

References

1. Wirth T, Parker N, Yl-Hertuala. History of gene therapy. Gene. 2013;252(2):62-169.2. Food and Drug Administration. FDA continues strong support of innovation in development of gene therapy products. Press release. Accessed July 1, 2021. https://www.fda.gov/news-events/press-announcements/fda-continues-strong-support-innovation-development-gene-therapy-products3. Science History Institute. James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin. Accessed July 1, 2021. https://www.sciencehistory.org/historical-profile/james-watson-francis-crick-maurice-wilkins-and-rosalind-franklin4. Nirenberg M. Historical review: Deciphering the genetic codea personal account. Trends Biochem Sci. 2004;29(1):46-54.5. Science History Institute. Herbert W Boyer and Stanley N Cohen. Accessed July 1, 2021. https://www.sciencehistory.org/historical-profile/herbert-w-boyer-and-stanley-n-cohen6. Sun M. Cline loses two NIH grants. Science. 1981;214(4525):1220.7. Blaese RM, Culver KW, Miller D, et al. T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science. 1995;270(5235):475-480.8. Kim YG, Cha J, Chandrasegaran S. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci U S A. 1996;93(3):1156-1160.9. Naldini L, Blomer U, Gallay P, et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996;272(5259):263-267.10. Sibbald B. Death but one unintended consequence of gene-therapy trial. CMAJ. 2001;164(11):1612.11. Hacein-Bey-Abina S, Garrigue A, Wang GP, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest. 2018;118(9):3132-3142.12. Cavazzana-Calvo M, Fischer A. Gene therapy for severe combined immunodeficiency: are we there yet? J Clin Invest. 2007;117(6):1456-1465.13. Humeau L. From the bench to the clinic: story and lessons from VRX496, the first lentivector ever tested in a phase 1 clinical trial. Presented at: Beilstein Bozen Symposium; May 15-May 19, 2006; Bozen, Italy.14. Pearson S, Jia H, Kandachi K. China approves first gene therapy. Nat Biotechnol. 2004;22(1):3-4. 15. Daley J. Gene therapy arrives. Nature. 2019;576:S12-S13.16. Maguire AM, High KA, Auricchio A, et al. Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial. Lancet. 2009;374(9701):1597-1605.17. Luxturna (voretigene neparvovec-ryzl) [prescribing information]. Philadelphia, PA: Spark Therapeutics, Inc.; 2017.18. Christian M, Cermak T, Doyle EL, et al. Targeting DNA double-strand breaks with TAL effector nucleases. Genetics. 2010;186(2):757-761.19. Cavazzana-Calvo M, Payen E, Negre O, et al. Transfusion independence and HMGA2 activation after gene therapy of human -thalassaemia. Nature. 2010;467(7313):318-322.20. Flemming A. Regulatory watch: Pioneering gene therapy on brink of approval. Nat Rev Drug Discov. 2012 ;11(9):664.21. Pharmaphorum. Glybera, the most expensive drug in the world, to be withdrawn after commercial flop. Accessed April 29, 2021. https://pharmaphorum.com/news/glybera-expensive-drug-world-withdrawn-commercial-flop/22. Cong L, Ran FA, Cox D, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819-823.23. Aiuti A, Roncarolo MG, Naldini L. Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products. EMBO Mol Med. 2017;9(6):737-740.24. Strimvelis Summary of Product Characteristics, GlaxoSmithKline (GSK); 2016.25. Food and Drug Administration. FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. Accessed April 27, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-car-t-cell-therapy-treat-adults-certain-types-large-b-cell-lymphoma26. European Medicines Agency. Yescarta. Accessed April 29, 2021. https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta27. Cross R. CRISPR is coming to the clinic this year. Chem Eng News. 2018;96(2):18-19.28. Food and Drug Administration. FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality. Accessed April 27, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease29. European Medicines Agency. Zolgensma. Accessed May 26, 2021. https://www.ema.europa.eu/en/medicines/human/EPAR/zolgensma30. European Medicines Agency. Zynteglo. Accessed April 29, 2021. https://www.ema.europa.eu/en/medicines/human/referrals/zynteglo31. Regulatory Affairs Professional Society. FDA finalizes 6 gene therapy guidances, unveils a new draft. Accessed April 27, 2021. https://www.raps.org/news-and-articles/news-articles/2020/1/fda-finalizes-6-gene-therapy-guidances-unveils-a 32. PR Newswire. 4-day-old baby receives life-changing $2M gene therapy at woman's hospital in Baton Rouge. Accessed April 27, 2021. https://www.prnewswire.com/news-releases/4-day-old-baby-receives-life-changing-2m-gene-therapy-at-womans-hospital-in-baton-rouge-301233580.html

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History of Gene Therapy | Discovery and Evolution

Cell and gene therapy: Biopharma portfolio strategy | McKinsey

The potential importance of cell and gene therapy (CGT) to healthcare and the biopharma industry seems clear. CGT accounts for just 1 percent of launched products in major markets, with treatment of the vast majority of diseases still using small-molecule drugs. Yet those productswhich include cell therapies, such as chimeric antigen receptor (CAR) T-cell therapy for aggressive B-cell lymphomas, and gene therapiesto treat a range of monogenic rare diseaseshave proved transformative for patients. And there are many more in development. As of February 2020, CGT products account for 12 percent of the industrys clinical pipeline and at least 16 percent of the preclinical pipeline, but as most manufacturers do not disclose their preclinical assets, the true figure may be considerably higher (Exhibit 1).

Exhibit 1

New CGT products will surely emerge from this pipeline upon the continuing discovery of indications that CGT can address and the growing industry understanding of the genetic drivers and determinants of more complex, multifactorial diseases. Indeed, the pace of CGT-asset development is similar to that of monoclonal-antibody (mAb) assets in that modalitys early years, and mAb therapy went on to transform the biopharma market (see sidebar, Cell and gene therapy: Mirroring monoclonal-antibody therapy).

Exciting clinical results are helping to propel this pace. Success rates for CGT products are higher than those for small-molecule products, probably because CGT tends to target specific disease drivers rather than the broad targets (with potential for off-target effects) of small-molecule therapy. The sample size of launched CGTs is small, so comparisons may change as the market evolves. Nevertheless, there is a marked difference thus far. Between 2008 and 2018, the R&D success rate from Phase I to launch for small-molecule products was 8.2 percent; for CGT products, it was 11 percent.

Recognizing CGTs potential, 16 of the worlds largest (by revenue) 20 biopharmacos now have CGT assets in their product portfolios. Yet most companies are moving cautiouslyonly two of the top 20 have CGT assets making up more than 20 percent of their pipelines. They are still considering whether, when, and how to reposition their portfolios. In the meantime, biotech companies remain leaders in CGT innovation.

As of February 2020, only a small percentage of launched CGT assets either originated from or are owned by a top 20 biopharmacoin both cases, only 15 percent of launched assetsindicating how much opportunity there is for such companies to increase their exposure to CGT assets (Exhibit 2).

Exhibit 2

The figures are not altogether surprising, given that biopharmacos expertise often lies in disease areas, not in the development of the technology platforms that generate CGT products. More often than not, the original research behind new platforms is conducted by academics (who go on to set up their own biotech companies) and investors (whose models include company origination because of the potential financial gains and the concentrated technical risk that platform investments carry). Venture-capital firms are more comfortable than established biopharmacos with such risks.

Nevertheless, given the growth potential of CGT and the promise it holds for patients, most large biopharmacos are considering increasing their presence in the market. This article is intended to help guide their decisions, describing the key considerations when assessing investment opportunities and the various entry strategiesas well as the trade-offs to be made when choosing among them.

There are many technology platforms in development that seek to address different challengesassociated with CGT. In cell therapy, work is afoot to improve the manufacture of autologous therapies to reduce the cost of goods sold or vein-to-vein time, enable breakthrough efficacy in solid tumors, and improve the patient or customer experience. In gene therapy, there are investment opportunities in platforms that aim to overcome the limitations of current vectors (such as the size of the transgene, suboptimal tropism, or the triggering of an immune response) that enable nonviral delivery methods, reduce manufacturing costs, and expand manufacturing capacity.

The decision, therefore, is about not only whether to increase investment in CGT but also which technology platforms or assets to back. Companies should thus assess each investment opportunity by both strategic fit and technology attractiveness. Strategic considerations on a CGT platform or asset include whether it complements a companys disease areas of focus, the internal pipeline would benefit from diversification with new modalities, and the company has the required capabilities, capital, and conviction.

A host of questions need to be asked to gauge the attractiveness of the technology. Has it demonstrated proof of concept? What risks remain? Does the company have enough understanding of the underlying mechanisms? Does the technology enable first-mover advantage? What are the intellectual-property considerations? Is the platform differentiated from competing platforms? And given the rapid pace of innovation in CGT, what is the risk that the technology platform quickly becomes obsolete?

CAR T-cell therapy, whereby a patients T cells are genetically engineered to express a chimeric antigen receptor that targets a specific tumor antigen, illustrates the potential risk. In a relatively short time, the field has progressed from an initial set of constructs to a second generation that has given rise to two FDA-approved products, YESCARTA and KYMRIAH, even as third- and fourth-generation products are in development.

Investment opportunities that have a strong strategic fit and high-potential technologythose that fall into the top-right quadrant shown in Exhibit 3will be attractive. For example, a CAR T-cell or T-cell-receptor platform would fall in the top right for many oncology-focused companies. In the absence of such opportunities, those in the top-left or bottom-right quadrants may still be worthwhile as a means of gaining exposure to CGT, perhaps through an early-stage investment. For example, next-generation, unproven gene-editing technologies may fall in the bottom-right quadrant for companies focused on rare diseases with known genetic drivers. Companies would have to be prepared to tolerate the associated risks, however, and not all will conclude that now is the time to make a move.

Exhibit 3

Once a manufacturer has decided that it makes strategic sense to invest in CGT and has identified an attractive technology, it must choose an entry strategy. There are three main options: build a proprietary platform, buy an existing platform or one or more of its assets, or form a partnership to gain access to assets on platforms developed by others (Exhibit 4). The three options have different profiles in the capital required, changes to the operational model needed, and risk (as measured by the degree of diversification offered across different technologies).

Exhibit 4

Companies that build a platform or platforms from scratch enjoy full control over development efforts and retain all the financial rewards of successful assets. They also get the chance to build their own CGT capabilitiesscientific, clinical, and commercialand have the freedom to adapt as the technology evolves. In return, they have to commit significant resources to internal R&D and will, in effect, be placing big, early bets on a single or very limited number of platforms. Additionally, they may need to make significant changes to operating models designed for traditional modalities.

Buying a developed platform or late-stage asset carries less technical risk (assuming robust early data), though invariably a price premium too. This means that few, if any, companies will be able to acquire a large number of them, so companies continue to bet on a single or limited number of platforms.

The third optionforming a partnership to gain access to assets on platforms that others have developedlies between these two extremes in investment cost and risk. Because partnerships in the still-nascent CGT sector are relatively cheap, biopharmacos can afford to spread their bets on where future success might lie through establishing several partnerships.

Accordingly, most biopharmacos to date have followed the partnership route when placing a stake in CGT. Between 2010 and 2014, there were a total of 16 M&A deals in the CGT space. That rose to more than 60 between 2015 and 2019. However, even in 2019, when M&A activity was strongest, partnerships accounted for more than 80 percent of total transaction activity (Exhibit 5).

Exhibit 5

Nearly all of the top 20 biopharmacos have formed at least one partnership, while ten have made an acquisition. Just one has built its own platform. Exhibit 6 details this, along with the impact that the deals have had on the composition of company pipelines.

Exhibit 6

Partnerships come in three main varieties: those that give a biopharmaco access to a single asset, those that give it access to all assets in selected therapeutic areas that might emerge from a platform, and those that give it access to all platform assets, regardless of the therapeutic area or indication.

Partnerships structured to give a biopharmaco access to a single asset are the simplest way to enter the CGT market and are often chosen by companies that have a strong focus on certain indications and believe that their competitive advantage lies in owning multiple therapies across modalities in that space. A single-asset partnership also minimizes the investment required. However, this kind of partnership may leave a biopharmaco having to introduce a new operating model for a single asset.

Partnerships structured to give a biopharmaco access to all assets from a platform in certain therapeutic areas can help companies with a strong strategic focus on a given therapeutic area strengthen their portfolios and build more expertise in that area. In addition, more assets in a new modality means more opportunity to build the relevant development and commercial expertise.

The third option, partnering to win access to all the assets in a particular modality generated by a platform, tends to be the partnership of choice for biopharmacos that believe future competitive advantage lies in access to the best technology, no matter what may be the associated indication or therapeutic area. Through such a partnership, a company can follow the science, developing the technology for the indications in which it can provide the most clinical benefit. Such a strategy requires more investment than other forms of partnership, however, and so carries more concentrated technology risk. Companies may also find themselves developing products for therapeutic areas in which they have no expertise and thus are at a competitive disadvantage.

In addition to these three kinds of partnerships with biotech companies, some biopharmacos are considering more innovative ways to allocate their limited resources across multiple CGT technologies in a manner that also boosts their chances of keeping pace with rapid innovation. By partnering with venture-capital firms or biotech originators to launch new assets, new platforms, or even new companies or by collaborating with large academic institutions to license multiple new technologies, they are making much earlier-stage bets on where future success might lie.

The CGT era is an exciting one for healthcare, and all biopharmacos will want to reassess their portfolio strategies to decide whether and to what extent to diversify their pipelines. Most big biopharmacos have chosen partnerships to explore CGT initially, though the likelihood is that many will use a combination of strategies to increase their exposure and access to several technologies as the market evolves. Yet whether a company is still testing the water or is ready to commit, it will need to think carefully about how it builds its exposure to the CGT market and be fully aware of how to assess each investment opportunity, the range of possible entry strategies, and the different advantages and risks that each carries.

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Cell and gene therapy: Biopharma portfolio strategy | McKinsey

Difference Between Ex Vivo and In Vivo Gene Therapy

Key Difference Ex Vivo vs In Vivo Gene Therapy

Gene therapy is an important technique which is used to treat or prevent genetic diseases by introducing genes for missing or defective genes. Certain diseases can be cured by inserting the healthy genes in place of mutated or missing genes responsible for the disease. Gene therapy is mostly applied for somatic cells than germline cells, and it can be categorized into two major types named Ex vivo gene therapy and In vivo gene therapy. The key difference between Ex vivo and In vivo gene therapy is that therapeutic genes are transferred to in vitro cell cultures and reintroduced into a patient in ex vivo gene therapy while genes are delivered directly to patients tissues or cells without culturing the cells in vitro in in vivo gene therapy.

CONTENTS1. Overview and Key Difference2. What is Ex Vivo Gene Therapy3. What is In Vivo Gene Therapy4. Side by Side Comparison Ex Vivo vs In Vivo Gene Therapy5. Summary

Ex vivo gene therapy is a type of gene therapy which involves exterior modification of a patients cell and reintroduction of it to the patient. The cells are cultured in the labs (outside the patients body), and genes are inserted. Then the stable transformants are selected and reintroduced into the patient to treat the disease. Ex vivo gene therapy can be applied only to certain cell types or selected tissues. Bone marrow cells are the cells frequently used for ex vivo gene therapy.

There are several major steps involved in Ex vivo gene therapy as follows;

In ex vivo gene therapy, carriers or vectors are used to deliver genes into target cells. Successful gene delivery is dependent on the carrier system, and the important vectors used in ex vivo gene therapy are viruses, bone marrow cells, human artificial chromosome, etc. Compared to the in vivo gene therapy, ex vivo gene therapy does not involve adverse immunological reactions in the patients body since the genetic correction is done in vitro. However, the success depends on stable incorporation and expression of the remedial gene within the patient body.

Figure 01: Ex vivo gene therapy

In vivo gene therapy is a technique which involves direct delivery of genes into the cells of a particular tissue inside the patients body to treat genetic diseases. It can be applied to many tissues of the human body including liver, muscle, skin, lung, spleen, brain, blood cells, etc. The therapeutic genes are introduced by the viral or nonviral-based vectors into the patient. However, the success depends on several factors such as efficient uptake of the therapeutic gene carrying vectors by the target cells, intracellular degradation of the genes within the target cells and gene uptake by the nucleus, expression ability of the gene, etc.

Figure 02: In vivo gene therapy

Therapeutic genes are introduced into patients body as a treatment for certain diseases. It is known as gene therapy and can be done in two ways namely ex vivo gene therapy and in vivo gene therapy. The difference between ex vivo and in vivo gene therapy is that gene insertion in ex vivo gene therapy is done in the cell cultures exterior to patients body and the corrected cells are reintroduced to the patient while in in vivo gene therapy genes are introduced directly into the interior target tissues without isolating the cells. The success of the both processes depends on the stable insertion and transformation of the therapeutic genes into the patient cells.

Reference:1.What is gene therapy? Genetics Home Reference. U.S. National Library of Medicine. National Institutes of Health, n.d. Web. 24 Apr. 2017.2.Evaluation of the Clinical Success of Ex Vivo and In Vivo Gene Therapy | JYI The Undergraduate Research Journal. JYI The Undergraduate Research Journal. N.p., n.d. Web. 24 Apr. 20173. Crystal, Ronald G. In vivo and ex vivo gene therapy strategies to treat tumors using adenovirus gene transfer vectors. SpringerLink. Springer-Verlag, n.d. Web. 24 Apr. 2017

Image Courtesy:1. ExVivoGeneTherapy plBy Pisum na podstawie pracy Lizanne Koch Own work (CC BY-SA 3.0) via Commons Wikimedia2. In vivo gene therapy pl By Pisum na podstawie pracy Lizanne Koch Own work (CC BY-SA 3.0) via Commons Wikimedia

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Difference Between Ex Vivo and In Vivo Gene Therapy

What is Gene Therapy? | FDA – U.S. Food and Drug Administration

Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1.

Gene therapy is a technique that modifies a persons genes to treat or cure disease. Gene therapies can work by several mechanisms:

Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.

There are a variety of types of gene therapy products, including:

Gene therapy products are biological products regulated by the FDAs Center for Biologics Evaluation and Research (CBER). Clinical studies in humans require the submission of an investigational new drug application (IND) prior to initiating clinical studies in the United States. Marketing a gene therapy product requires submission and approval of a biologics license application (BLA).

Long Term Follow-Up After Administration of Human Gene Therapy Products; Guidance for Industry, January 2020

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What is Gene Therapy? | FDA - U.S. Food and Drug Administration

Gene Therapy Gel Offers New Hope Against Rare Blistering Disease

THURSDAY, Dec. 15, 2022 (HealthDay News) -- An experimental gene therapy that's applied as a skin gel appears to heal wounds caused by a rare and severe genetic skin disease.

Experts called the findings "remarkable," and said they bring hope of a better quality of life to children and young adults living with the condition, called dystrophic epidermolysis bullosa (DEB).

The disease affects about 3 out of every 1 million people. It's caused by a flawed gene that renders the body unable to produce a particular collagen -- a "glue" between the skin layers that is essential to its strength and integrity.

Kids born with DEB are sometimes called "butterfly children" because their skin is so fragile, even an ordinary bump or friction can cause blistering that progresses to painful open wounds.

In the most severe cases, infants have blisters or missing skin at birth, or soon after. Those children typically develop widespread scarring over their bodies and can have eye inflammation that impairs their vision. Blisters and scarring also arise along the lining of the mouth, throat and digestive tract -- which can interfere with eating and cause malnutrition.

As young adults, people with DEB face a high risk of squamous cell carcinoma, a form of skin cancer that is normally highly curable, but in a person with DEB often proves deadly.

There has never been any specific treatment for DEB. Managing it is all about wound care, preventing infections, trying to relieve pain and other "supportive" therapies, said Dr. Peter Marinkovich, the senior researcher on the new study.

"We're helplessly watching blisters and wounds form, without any way to stop them," said Marinkovich, who directs Stanford University's Blistering Disease Clinic.

The new gene therapy, delivered by a skin gel applied directly to wounds, could become the first treatment for the rare disease. Krystal Biotech, the product's developer, has submitted an application for approval to the U.S. Food and Drug Administration, and said the agency granted it "priority review" designation.

The therapy does not correct the genetic flaw causing DEB, or cure the disease.

Instead, the gel contains a modified herpes virus that delivers two functioning copies of the gene, called COL7A1, to patients' skin cells. The cells are then able to produce the missing collagen protein -- with the goal of healing wounds.

In the new trial, published Dec. 15 in the New England Journal of Medicine, Marinkovich and his team found the approach did just that.

The study involved 31 children and adults with DEB. Each patient had one wound treated with the gene therapy gel, and a second, similar wound treated with a placebo (inactive) gel. In all cases, it was applied during weekly bandage changes.

After six months, 67% of wounds treated with the gene therapy were completely closed, versus 22% of those treated with the placebo gel. That included healing of longstanding -- even 10-year-old -- wounds, according to Marinkovich.

Other experts called the trial "pivotal," and said that if the therapy continues to have such benefits over the long term, it could have a "transformational" impact on patients' quality of life.

"This is a devastating disease," said Dr. Aimee Payne, a professor of dermatology at the University of Pennsylvania.

Payne, who wrote an editorial published with the study, said that various high-tech treatments for DEB have been attempted -- including stem cell therapies and skin grafts.

"And now this comes along, and it's a salve that you put on the skin," Payne said. "It almost seems magical."

The notion of topical treatments is new to the gene therapy field, said David Schaffer, a professor of chemical and biomolecular engineering at the University of California, Berkeley.

A limitation of the approach is that it's transient, explained Schaffer, who wrote a separate editorial published with the study. As skin cells naturally die, the functioning COL7A1 gene is lost, too.

So the topical therapy will likely need to be repeated indefinitely. In addition, it does not penetrate the skin, Schaffer said. That means while it can be applied as needed to new wounds, it cannot prevent them.

That said, a gel capable of closing wounds could transform patients' lives, according to Schaffer. And if that healing is ultimately shown to prevent squamous cell carcinoma, he said, "that would be huge."

As for safety, the trial found no serious side effects. A theoretical concern, the experts said, is that the immune system could react against the herpes simplex virus used in the gel, or the newly produced collagen protein.

The herpes virus is genetically modified so that it cannot replicate or spread in the body. But because the virus is naturally adept at evading the immune system, Marinkovich explained, it's a good vehicle for delivering the COL7A1 gene to cells without sparking an immune response.

The skin gel does not address the internal lesions that DEB causes. But, Marinkovich said, it's possible the same gene therapy could be delivered to those areas of the body by other means -- drops for the eyes, an oral "swish" for the mouth, or suppositories for anal lesions.

Among the ongoing research steps, he said, is to treat skin lesions in younger children, as early as 6 months of age, to see if that can prevent extensive skin scarring.

Schaffer pointed to the bigger picture. Gene therapy, he said, has long been "held back" by a lack of good delivery systems. But that's changing. Just last month, Schaffer noted, the first gene therapy for hemophilia B -- delivered by a single IV infusion -- was approved by the FDA.

"Gene therapy is beginning to work," he said.

More information

The nonprofit DEBRA has more on the different forms of epidermolysis bullosa.

SOURCES: M. Peter Marinkovich, MD, associate professor, dermatology, and director, Blistering Disease Clinic, Stanford University School of Medicine; Aimee S. Payne, MD, PhD, professor, dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia; David V. Schaffer, PhD, professor, chemical and biomolecular engineering, bioengineering, molecular and cell biology, University of California, Berkeley; New England Journal of Medicine, Dec. 15, 2022

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Gene Therapy Gel Offers New Hope Against Rare Blistering Disease

KeyboardEvent.keyCode – Web APIs | MDN – Mozilla

DOM_VK_CANCEL 0x03 (3) Cancel key. DOM_VK_HELP 0x06 (6) Help key. DOM_VK_BACK_SPACE 0x08 (8) Backspace key. DOM_VK_TAB 0x09 (9) Tab key. DOM_VK_CLEAR 0x0C (12) "5" key on Numpad when NumLock is unlocked. Or on Mac, clear key which is positioned at NumLock key. DOM_VK_RETURN 0x0D (13) Return/enter key on the main keyboard. DOM_VK_ENTER 0x0E (14) Reserved, but not used. Deprecated (Dropped, see bug969247.) DOM_VK_SHIFT 0x10 (16) Shift key. DOM_VK_CONTROL 0x11 (17) Control key. DOM_VK_ALT 0x12 (18) Alt (Option on Mac) key. DOM_VK_PAUSE 0x13 (19) Pause key. DOM_VK_CAPS_LOCK 0x14 (20) Caps lock. DOM_VK_KANA 0x15 (21) Linux support for this keycode was added in Gecko 4.0. DOM_VK_HANGUL 0x15 (21) Linux support for this keycode was added in Gecko 4.0. DOM_VK_EISU 0x 16 (22) "" key on Japanese Mac keyboard. DOM_VK_JUNJA 0x17 (23) Linux support for this keycode was added in Gecko 4.0. DOM_VK_FINAL 0x18 (24) Linux support for this keycode was added in Gecko 4.0. DOM_VK_HANJA 0x19 (25) Linux support for this keycode was added in Gecko 4.0. DOM_VK_KANJI 0x19 (25) Linux support for this keycode was added in Gecko 4.0. DOM_VK_ESCAPE 0x1B (27) Escape key. DOM_VK_CONVERT 0x1C (28) Linux support for this keycode was added in Gecko 4.0. DOM_VK_NONCONVERT 0x1D (29) Linux support for this keycode was added in Gecko 4.0. DOM_VK_ACCEPT 0x1E (30) Linux support for this keycode was added in Gecko 4.0. DOM_VK_MODECHANGE 0x1F (31) Linux support for this keycode was added in Gecko 4.0. DOM_VK_SPACE 0x20 (32) Space bar. DOM_VK_PAGE_UP 0x21 (33) Page Up key. DOM_VK_PAGE_DOWN 0x22 (34) Page Down key. DOM_VK_END 0x23 (35) End key. DOM_VK_HOME 0x24 (36) Home key. DOM_VK_LEFT 0x25 (37) Left arrow. DOM_VK_UP 0x26 (38) Up arrow. DOM_VK_RIGHT 0x27 (39) Right arrow. DOM_VK_DOWN 0x28 (40) Down arrow. DOM_VK_SELECT 0x29 (41) Linux support for this keycode was added in Gecko 4.0. DOM_VK_PRINT 0x2A (42) Linux support for this keycode was added in Gecko 4.0. DOM_VK_EXECUTE 0x2B (43) Linux support for this keycode was added in Gecko 4.0. DOM_VK_PRINTSCREEN 0x2C (44) Print Screen key. DOM_VK_INSERT 0x2D (45) Ins(ert) key. DOM_VK_DELETE 0x2E (46) Del(ete) key. DOM_VK_0 0x30 (48) "0" key in standard key location. DOM_VK_1 0x31 (49) "1" key in standard key location. DOM_VK_2 0x32 (50) "2" key in standard key location. DOM_VK_3 0x33 (51) "3" key in standard key location. DOM_VK_4 0x34 (52) "4" key in standard key location. DOM_VK_5 0x35 (53) "5" key in standard key location. DOM_VK_6 0x36 (54) "6" key in standard key location. DOM_VK_7 0x37 (55) "7" key in standard key location. DOM_VK_8 0x38 (56) "8" key in standard key location. DOM_VK_9 0x39 (57) "9" key in standard key location. DOM_VK_COLON 0x3A (58) Colon (":") key. DOM_VK_SEMICOLON 0x3B (59) Semicolon (";") key. DOM_VK_LESS_THAN 0x3C (60) Less-than ("<") key. DOM_VK_EQUALS 0x3D (61) Equals ("=") key. DOM_VK_GREATER_THAN 0x3E (62) Greater-than (">") key. DOM_VK_QUESTION_MARK 0x3F (63) Question mark ("?") key. DOM_VK_AT 0x40 (64) Atmark ("@") key. DOM_VK_A 0x41 (65) "A" key. DOM_VK_B 0x42 (66) "B" key. DOM_VK_C 0x43 (67) "C" key. DOM_VK_D 0x44 (68) "D" key. DOM_VK_E 0x45 (69) "E" key. DOM_VK_F 0x46 (70) "F" key. DOM_VK_G 0x47 (71) "G" key. DOM_VK_H 0x48 (72) "H" key. DOM_VK_I 0x49 (73) "I" key. DOM_VK_J 0x4A (74) "J" key. DOM_VK_K 0x4B (75) "K" key. DOM_VK_L 0x4C (76) "L" key. DOM_VK_M 0x4D (77) "M" key. DOM_VK_N 0x4E (78) "N" key. DOM_VK_O 0x4F (79) "O" key. DOM_VK_P 0x50 (80) "P" key. DOM_VK_Q 0x51 (81) "Q" key. DOM_VK_R 0x52 (82) "R" key. DOM_VK_S 0x53 (83) "S" key. DOM_VK_T 0x54 (84) "T" key. DOM_VK_U 0x55 (85) "U" key. DOM_VK_V 0x56 (86) "V" key. DOM_VK_W 0x57 (87) "W" key. DOM_VK_X 0x58 (88) "X" key. DOM_VK_Y 0x59 (89) "Y" key. DOM_VK_Z 0x5A (90) "Z" key. DOM_VK_WIN 0x5B (91) Windows logo key on Windows. Or Super or Hyper key on Linux. DOM_VK_CONTEXT_MENU 0x5D (93) Opening context menu key. DOM_VK_SLEEP 0x5F (95) Linux support for this keycode was added in Gecko 4.0. DOM_VK_NUMPAD0 0x60 (96) "0" on the numeric keypad. DOM_VK_NUMPAD1 0x61 (97) "1" on the numeric keypad. DOM_VK_NUMPAD2 0x62 (98) "2" on the numeric keypad. DOM_VK_NUMPAD3 0x63 (99) "3" on the numeric keypad. DOM_VK_NUMPAD4 0x64 (100) "4" on the numeric keypad. DOM_VK_NUMPAD5 0x65 (101) "5" on the numeric keypad. DOM_VK_NUMPAD6 0x66 (102) "6" on the numeric keypad. DOM_VK_NUMPAD7 0x67 (103) "7" on the numeric keypad. DOM_VK_NUMPAD8 0x68 (104) "8" on the numeric keypad. DOM_VK_NUMPAD9 0x69 (105) "9" on the numeric keypad. DOM_VK_MULTIPLY 0x6A (106) "*" on the numeric keypad. DOM_VK_ADD 0x6B (107) "+" on the numeric keypad. DOM_VK_SEPARATOR 0x6C (108) DOM_VK_SUBTRACT 0x6D (109) "-" on the numeric keypad. DOM_VK_DECIMAL 0x6E (110) Decimal point on the numeric keypad. DOM_VK_DIVIDE 0x6F (111) "/" on the numeric keypad. DOM_VK_F1 0x70 (112) F1 key. DOM_VK_F2 0x71 (113) F2 key. DOM_VK_F3 0x72 (114) F3 key. DOM_VK_F4 0x73 (115) F4 key. DOM_VK_F5 0x74 (116) F5 key. DOM_VK_F6 0x75 (117) F6 key. DOM_VK_F7 0x76 (118) F7 key. DOM_VK_F8 0x77 (119) F8 key. DOM_VK_F9 0x78 (120) F9 key. DOM_VK_F10 0x79 (121) F10 key. DOM_VK_F11 0x7A (122) F11 key. DOM_VK_F12 0x7B (123) F12 key. DOM_VK_F13 0x7C (124) F13 key. DOM_VK_F14 0x7D (125) F14 key. DOM_VK_F15 0x7E (126) F15 key. DOM_VK_F16 0x7F (127) F16 key. DOM_VK_F17 0x80 (128) F17 key. DOM_VK_F18 0x81 (129) F18 key. DOM_VK_F19 0x82 (130) F19 key. DOM_VK_F20 0x83 (131) F20 key. DOM_VK_F21 0x84 (132) F21 key. DOM_VK_F22 0x85 (133) F22 key. DOM_VK_F23 0x86 (134) F23 key. DOM_VK_F24 0x87 (135) F24 key. DOM_VK_NUM_LOCK 0x90 (144) Num Lock key. DOM_VK_SCROLL_LOCK 0x91 (145) Scroll Lock key. DOM_VK_WIN_OEM_FJ_JISHO 0x92 (146) An OEM specific key on Windows. This was used for "Dictionary" key on Fujitsu OASYS. DOM_VK_WIN_OEM_FJ_MASSHOU 0x93 (147) An OEM specific key on Windows. This was used for "Unregister word" key on Fujitsu OASYS. DOM_VK_WIN_OEM_FJ_TOUROKU 0x94 (148) An OEM specific key on Windows. This was used for "Register word" key on Fujitsu OASYS. DOM_VK_WIN_OEM_FJ_LOYA 0x95 (149) An OEM specific key on Windows. This was used for "Left OYAYUBI" key on Fujitsu OASYS. DOM_VK_WIN_OEM_FJ_ROYA 0x96 (150) An OEM specific key on Windows. This was used for "Right OYAYUBI" key on Fujitsu OASYS. DOM_VK_CIRCUMFLEX 0xA0 (160) Circumflex ("^") key. DOM_VK_EXCLAMATION 0xA1 (161) Exclamation ("!") key. DOM_VK_DOUBLE_QUOTE 0xA3 (162) Double quote (""") key. DOM_VK_HASH 0xA3 (163) Hash ("#") key. DOM_VK_DOLLAR 0xA4 (164) Dollar sign ("$") key. DOM_VK_PERCENT 0xA5 (165) Percent ("%") key. DOM_VK_AMPERSAND 0xA6 (166) Ampersand ("&") key. DOM_VK_UNDERSCORE 0xA7 (167) Underscore ("_") key. DOM_VK_OPEN_PAREN 0xA8 (168) Open parenthesis ("(") key. DOM_VK_CLOSE_PAREN 0xA9 (169) Close parenthesis (")") key. DOM_VK_ASTERISK 0xAA (170) Asterisk ("*") key. DOM_VK_PLUS 0xAB (171) Plus ("+") key. DOM_VK_PIPE 0xAC (172) Pipe ("|") key. DOM_VK_HYPHEN_MINUS 0xAD (173) Hyphen-US/docs/Minus ("-") key. DOM_VK_OPEN_CURLY_BRACKET 0xAE (174) Open curly bracket ("{") key. DOM_VK_CLOSE_CURLY_BRACKET 0xAF (175) Close curly bracket ("}") key. DOM_VK_TILDE 0xB0 (176) Tilde ("~") key. DOM_VK_VOLUME_MUTE 0xB5 (181) Audio mute key. DOM_VK_VOLUME_DOWN 0xB6 (182) Audio volume down key DOM_VK_VOLUME_UP 0xB7 (183) Audio volume up key DOM_VK_COMMA 0xBC (188) Comma (",") key. DOM_VK_PERIOD 0xBE (190) Period (".") key. DOM_VK_SLASH 0xBF (191) Slash ("/") key. DOM_VK_BACK_QUOTE 0xC0 (192) Back tick ("`") key. DOM_VK_OPEN_BRACKET 0xDB (219) Open square bracket ("[") key. DOM_VK_BACK_SLASH 0xDC (220) Back slash ("") key. DOM_VK_CLOSE_BRACKET 0xDD (221) Close square bracket ("]") key. DOM_VK_QUOTE 0xDE (222) Quote (''') key. DOM_VK_META 0xE0 (224) Meta key on Linux, Command key on Mac. DOM_VK_ALTGR 0xE1 (225) AltGr key (Level 3 Shift key or Level 5 Shift key) on Linux. DOM_VK_WIN_ICO_HELP 0xE3 (227) An OEM specific key on Windows. This is (was?) used for Olivetti ICO keyboard. DOM_VK_WIN_ICO_00 0xE4 (228) An OEM specific key on Windows. This is (was?) used for Olivetti ICO keyboard. DOM_VK_WIN_ICO_CLEAR 0xE6 (230) An OEM specific key on Windows. This is (was?) used for Olivetti ICO keyboard. DOM_VK_WIN_OEM_RESET 0xE9 (233) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_JUMP 0xEA (234) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_PA1 0xEB (235) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_PA2 0xEC (236) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_PA3 0xED (237) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_WSCTRL 0xEE (238) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_CUSEL 0xEF (239) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_ATTN 0xF0 (240) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_FINISH 0xF1 (241) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_COPY 0xF2 (242) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_AUTO 0xF3 (243) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_ENLW 0xF4 (244) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_WIN_OEM_BACKTAB 0xF5 (245) An OEM specific key on Windows. This was used for Nokia/Ericsson's device. DOM_VK_ATTN 0xF6 (246) Attn (Attention) key of IBM midrange computers, e.g., AS/400. DOM_VK_CRSEL 0xF7 (247) CrSel (Cursor Selection) key of IBM 3270 keyboard layout. DOM_VK_EXSEL 0xF8 (248) ExSel (Extend Selection) key of IBM 3270 keyboard layout. DOM_VK_EREOF 0xF9 (249) Erase EOF key of IBM 3270 keyboard layout. DOM_VK_PLAY 0xFA (250) Play key of IBM 3270 keyboard layout. DOM_VK_ZOOM 0xFB (251) Zoom key. DOM_VK_PA1 0xFD (253) PA1 key of IBM 3270 keyboard layout. DOM_VK_WIN_OEM_CLEAR 0xFE (254) Clear key, but we're not sure the meaning difference from DOM_VK_CLEAR.

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KeyboardEvent.keyCode - Web APIs | MDN - Mozilla