Takeaways

Scientists have made progress growing human liver in the lab.

The challenge has been to direct stems cells to grow into a mature, functioning adult organ.

This study shows that stem cells can be programmed, using genetic engineering, to grow from immature cells into mature tissue.

When a tiny lab-grown liver was transplanted into mice with liver disease, it extended the lives of the sick animals.

Imagine if researchers could program stem cells, which have the potential to grow into all cell types in the body, so that they could generate an entire human organ. This would allow scientists to manufacture tissues for testing drugs and reduce the demand for transplant organs by having new ones grown directly from a patients cells.

Im a researcher working in this new field called synthetic biology focused on creating new biological parts and redesigning existing biological systems. In a new paper, my colleagues and I showed progress in one of the key challenges with lab-grown organs figuring out the genes necessary to produce the variety of mature cells needed to construct a functioning liver.

Induced pluripotent stem cells, a subgroup of stem cells, are capable of producing cells that can build entire organs in the human body. But they can do this job only if they receive the right quantity of growth signals at the right time from their environment. If this happens, they eventually give rise to different cell types that can assemble and mature in the form of human organs and tissues.

The tissues researchers generate from pluripotent stem cells can provide a unique source for personalized medicine from transplantation to novel drug discovery.

But unfortunately, synthetic tissues from stem cells are not always suitable for transplant or drug testing because they contain unwanted cells from other tissues, or lack the tissue maturity and a complete network of blood vessels necessary for bringing oxygen and nutrients needed to nurture an organ. That is why having a framework to assess whether these lab-grown cells and tissues are doing their job, and how to make them more like human organs, is critical.

Inspired by this challenge, I was determined to establish a synthetic biology method to read and write, or program, tissue development. I am trying to do this using the genetic language of stem cells, similar to what is used by nature to form human organs.

I am a researcher specializing in synthetic biology and biological engineering at the Pittsburgh Liver Research Center and McGowan Institute for Regenerative Medicine, where the goals are to use engineering approaches to analyze and build novel biological systems and solve human health problems. My lab combines synthetic biology and regenerative medicine in a new field that strives to replace, regrow or repair diseased organs or tissues.

I chose to focus on growing new human livers because this organ is vital for controlling most levels of chemicals like proteins or sugar in the blood. The liver also breaks down harmful chemicals and metabolizes many drugs in our body. But the liver tissue is also vulnerable and can be damaged and destroyed by many diseases, such as hepatitis or fatty liver disease. There is a shortage of donor organs, which limits liver transplantation.

To make synthetic organs and tissues, scientists need to be able to control stem cells so that they can form into different types of cells, such as liver cells and blood vessel cells. The goal is to mature these stem cells into miniorgans, or organoids, containing blood vessels and the correct adult cell types that would be found in a natural organ.

One way to orchestrate maturation of synthetic tissues is to determine the list of genes needed to induce a group of stem cells to grow, mature and evolve into a complete and functioning organ. To derive this list I worked with Patrick Cahan and Samira Kiani to first use computational analysis to identify genes involved in transforming a group of stem cells into a mature functioning liver. Then our team led by two of my students Jeremy Velazquez and Ryan LeGraw used genetic engineering to alter specific genes we had identified and used them to help build and mature human liver tissues from stem cells.

The tissue is grown from a layer of genetically engineered stem cells in a petri dish. The function of genetic programs together with nutrients is to orchestrate formation of liver organoids over the course of 15 to 17 days.

I and my colleagues first compared the active genes in fetal liver organoids we had grown in the lab with those in adult human livers using a computational analysis to get a list of genes needed for driving fetal liver organoids to mature into adult organs.

We then used genetic engineering to tweak genes and the resulting proteins that the stem cells needed to mature further toward an adult liver. In the course of about 17 days we generated tiny several millimeters in width but more mature liver tissues with a range of cells typically found in livers in the third trimester of human pregnancies.

Like a mature human liver, these synthetic livers were able to store, synthesize and metabolize nutrients. Though our lab-grown livers were small, we are hopeful that we can scale them up in the future. While they share many similar features with adult livers, they arent perfect and our team still has work to do. For example, we still need to improve the capacity of the liver tissue to metabolize a variety of drugs. We also need to make it safer and more efficacious for eventual application in humans.

[Deep knowledge, daily. Sign up for The Conversations newsletter.]

Our study demonstrates the ability of these lab livers to mature and develop a functional network of blood vessels in just two and a half weeks. We believe this approach can pave the path for the manufacture of other organs with vasculature via genetic programming.

The liver organoids provide several key features of an adult human liver such as production of key blood proteins and regulation of bile a chemical important for digestion of food.

When we implanted the lab-grown liver tissues into mice suffering from liver disease, it increased the life span. We named our organoids designer organoids, as they are generated via a genetic design.

Mo Ebrahimkhani, Associate Professor of Pathology and Bioengineering, University of Pittsburgh

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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See more here:
Genetic engineering transformed stem cells into working ...

Every cell in your body has around 3 billion base pairs of DNA code inside it. Just a few small errors in this code could leave someone with a debilitating illness. Molecular biologist Eric Olsen has described it as equivalent to misspelling one word in a stack of one thousand bibles, and this tiny typo could put a child in a wheelchair for life.

Researchers have already identified DNA errors as the cause of nearly 7,000 diseases. Thankfully, the growing world of genome editing could be the "spell-checker" needed to detect and eventually fix these problems.

Genome editing is often equated with designer babies and CRISPR/Cas9. However, the world of genome editing is far more diverse and complex and goes well beyond just CRISPR, which is only the latest in a long line of editing "tools". Genome engineering is a type of genetic engineering in which DNA is inserted, deleted, modified, or replaced in the genome of a living organism.

It is an incredibly powerful tool with tremendous potential in the field of medicine. In its simplest form, it is a way of making specific changes to the DNA of an organism. It's similar to editing the code in a piece of computer software.

There is a reason why there is a lot of hype around gene editing, and you should be excited too. Genome editing could potentially be used to treat major degenerative diseases and fix simple genetic conditions like muscular dystrophy. It may one day soon be used to grow new human organs in pigs, combat the constant demand for organ transplants, and potentially turn human reproduction on its head, yes, we're talking about using it to engineer entire populations.

We are still a ways away from the movie Gattaca, or Aldous Huxley's Brave New World. Nonetheless, real-world gene engineering poses some very interesting ethical questions. Today we are going to look at the history of genome editing, new methods like CRISPR, as well as alternatives, and look at some of the ethical questions currently plaguing this medical tool.

Okay, to review, genome editing or gene editing is a relatively new method that lets scientists change the DNA from bacteria to animals. These "edits" could potentially lead to changes in physical traits like eye color, or, more importantly, to cure certain diseases. Genome editing has already been used in agriculture to modify crops to improve their yields and increase their resistance to disease and drought.

There are many different methods and technologies used to edit DNA. Nonetheless, most of these technologies generally act like the "cutting" and "pasting" functions on your computer, allowing scientists to alter the DNA at a specific spot in an organisms' genome. Though much of the hype around gene editing centers around its power to engineer humans, the main application of genome editing so far has been in plants and some animals in lab settings.

Once it was realized in the 1940s that DNA was responsible for heredity, and once the structure of the DNA molecule was elucidated in the 1950s,researchers realized that errors in this genetic code were responsible for many diseases and inherited conditions.

The question that followed was an obvious one. Could these errors be corrected? This question led to the emergence of genetic engineering in the 1970s, where new genetic code was introduced into organisms' DNA. However, this technology was not initially capable of inserting the new material in a highly targeted way.

One early example of targeting genes to certain sites within a genome of an organism usedhomologous recombination. This method involves the construction of a sort of template that matched the targeted genome sequence, and relied on the normal cell processes to insert this template at the correct location. The method was successfully used to introduce genetic modifications in mice using embryonic stem cells.

Another early method used conditional targeting using enzymes calledsite-specific recombinases(SSR). These techniques were able toknock out or switch on genes only in certain cells and ultimately allowed researchers to induce recombination under certain conditions, allowing genes to be knocked out or expressed at particular times or at particular stages of development.

The key to genome editing is creating a double-stranded break(DSB) in the genome at a specific point and removing the erroneous part of the genetic code. Enzymes are then used to repair the break, rejoining the ends of the DNA or to insert the missing correct sequences in the correct location. However, while certainenzymes are effective at cutting DNA, they generally cut at several multiple sites - potentially removing DNA that researchers do not want removed. To overcome this challenge, several types of nucleases (enzymes) have been created. These are called Zinc finger nucleases (ZFNs), transcription-activator like effector nucleases (TALEN), meganucleases, and the clustered regularly interspaced short palindromic repeats (CRISPR/Cas9).

Meganucleases werediscovered in the late 1980s, they canrecognize and cut DNA sequences of between 14 and 40 base pairs. However, it can be difficult to engineer nucleases that will cut the DNA at the exact site needed. Recently, a library of sorts has been created that has allowed scientists to more easily create meganucleases that will cut in specific locations. For example, there are now meganucleases able to remove mutations to the human XPC gene which causeXeroderma pigmentosum, a disorder that predisposes the patients to skin cancer and burns when exposed to UV light.

In the 1990s, scientists used zinc-finger nucleases to improve existing gene-editing techniques. These synthetic proteins are used for gene targeting and are composed of DNA-cutting endonuclease domains fused to zinc finger domains engineered to bind a specific DNA sequence. They can be used to add or delete cut sites in the genomes of cells. Though this method has been dramatically improved, the success rate is still only about 10 percent. Even more so, this gene-editing method is costly and time-consuming to design.

Transcription activator-like effector nucleases (TALEN) share some similarities to Zinc-finger nucleases. Developed in 2009, TALENs are engineered from proteins found in nature and are capable of binding to specific DNA sequences. And while their effectiveness and efficiency parallel ZFN, they are far easier to engineer.

While ZFN and TALEN do offer effective genome editing, one drawback is that they are both time-consuming and expensive to develop. And, the process of engineering proteins is prone to error. CRISPR is so revolutionary in gene editing realms because it offers scientists a faster and simpler way to edit the genome, "with little assembly required." CRISPR/Cas9 was already on the radar of researchers in the 1990s, but its full potential was not realized until recent years.

CRISPR/Cas9 is a powerful new gene-editing technology developed separately in around 2012 by scientists Feng Zhang, Jennifer Doudna, and Emmanuelle Charpentier.

CRISPR can recognize specific genome sequences and cut them often utilizing the Cas9 protein.

CRISPR technology is based on a defense mechanism that bacteria use to fight viruses. Viruses attack cells by using the cells' own machinery to create replicas of themselves. Eventually, the cell bursts and the virus copies are released into the organism to infect new cells. However, bacteria have evolved a way to fight back by cutting up the virus' DNA. If a bacteria survives a virus attack, they copy pieces of that virus' DNA and incorporate these into its own genomes. These copies are used like mugshots to allow the bacteria to identify harmful viruses.

To keep track of this collection of "mugshots" and to keep them separate from the bacteria's own DNA, repetitive sequences of molecules are placed around each sequence that was taken from a virus. When a bacteria comes up against a virus with a sequence in its collection, the bacteria sends an enzyme to cut ap
art and destroy anything that matches the genetic mugshot. CRISPR allows scientists to use a similar approach, often using the protein Cas9 to cut and replace specific gene sequences.

The CRISPR technique allows scientists to quickly and efficiently alter almost any gene in any plant or animal at a low cost. Researchers already have used the technique to correct genetic diseases in animals, grow crops more resilient to a certain climate, alter pig organs for easier human transplantation, sterilize mosquitos for disease prevention, and add muscle mass to beagles.

Scientists are also able to use CRISPR to create short RNA templates that match a targeted sequence in the genome, making the process of editing far easier, efficient, cheaper, and quicker. CRISPR is currently being used to develop treatments for HIV, Duchenne muscular dystrophy, some types of blindness, and Lyme disease just to name a few.

"CRISPR is incredibly powerful. It has already brought a revolution to the day-to-day life in most laboratories. I am very hopeful that over the next decade gene editing will transition from being a primarily research tool to something that enables new treatments in the clinic,"saidNeville Sanjana, of the New York Genome Center and an assistant professor of biology, neuroscience, and physiology at New York University.

Gene-editingtools like CRISPRcould give scientists the keys to the DNA kingdom, allowing us to find "molecular mistakes" and remove them. According to Nicola Patron, a molecular and synthetic biologist at the Earlham Institute in the UK, "We are getting to a point where we can investigate different combinations of genes, control when, where, and how much they are expressed, and investigate the roles of individual bases of DNA. Understanding what DNA sequences do is what enables us to solve problems in every field of biology from curing human diseases, to growing enough healthy food, to discovering and making new medicines, to understand why some species are going extinct."

Researchers could one day remove malaria from mosquitoes. Researchers have already created mosquitoes that are resistant to malaria by deleting a specific segment of mosquitoes' DNA. Neurodegenerative diseases like Alzheimer's and Parkinson's could potentially become a thing of the past. Scientists are already working on CRISPR-based platforms to identify the genes controlling the cellular processes that lead to neurodegenerative diseases. In 2017, researchers used CRISPR to shut down the HIV virus' ability to replicate, eliminating the HIV virus from infected cells.

In 2016, a lung cancer patient in China became the first human to receive an injection of cells that had been modified using CRISPR. Researchers used CRISPR to disable a gene used by the cancer cells to divide and multiply. Without the gene, researchers hope the cancer cells will not multiply.

From agriculture to pharmaceuticals, gene editing could one day help us build a better world.

Yes and no. Designer babies seem to lead the conversation when discussing CRISPR. Ethical questions like, "Is it okay to use gene therapy on an embryo when it is impossible to get permission from the embryo for treatment?" or "What if gene therapies are too expensive and only wealthy people can access and afford them?" lay at the core of most people's concerns.

What if people use these tools to improve a child's athletic ability or height rather than use it for treating diseases?

Would this lead to genetic discrimination? Though researchers are still navigating the arguments for and against, gene editing in humans has already begun.

The US, China, andthe UKhave approved gene editing in humans for research purposes only.

Even popular gene-editing tools like CRISPR are still not perfect. In some cases, the gene-editing tools make cuts in the wrong places, and researchers are still not 100% sure how that will affect people. Properly addressing the ethical concerns and ensuring gene editing safety are still two massive mountains that scientists need to climb before we see mainstream genome treatments.

In her book, A Crack in Creation: The New Power to Control Evolution,Jennifer A. Doudas paints us a picture of a gene-edited world, stating, "Tomatoes that can sit in the pantry slowly ripening for months without rotting. Plants that can weather climate change better. Mosquitoes that are unable to transmit malaria. Ultra-muscular dogs that make fearsome partners for police and soldiers. Cows that no longer grow horns."

She adds: "These organisms might sound far-fetched, but in fact, they already exist, thanks to gene editing. And they're only the beginning. As I write this, the world around us is being revolutionized by CRISPR, whether we're ready for it or not."

It does not sound too bad, right? What is your opinion on gene-editing? How will it change the world?

See the article here:
Everything You Need to Know About Genome Editing - Interesting Engineering

Takeaways

Scientists have made progress growing human liver in the lab.

The challenge has been to direct stems cells to grow into a mature, functioning adult organ.

This study shows that stem cells can be programmed, using genetic engineering, to grow from immature cells into mature tissue.

When a tiny lab-grown liver was transplanted into mice with liver disease, it extended the lives of the sick animals.

Imagine if researchers could program stem cells, which have the potential to grow into all cell types in the body, so that they could generate an entire human organ. This would allow scientists to manufacture tissues for testing drugs and reduce the demand for transplant organs by having new ones grown directly from a patients cells.

Im a researcher working in this new field called synthetic biology focused on creating new biological parts and redesigning existing biological systems. In a new paper, my colleagues and I showed progress in one of the key challenges with lab-grown organs figuring out the genes necessary to produce the variety of mature cells needed to construct a functioning liver.

Induced pluripotent stem cells, a subgroup of stem cells, are capable of producing cells that can build entire organs in the human body. But they can do this job only if they receive the right quantity of growth signals at the right time from their environment. If this happens, they eventually give rise to different cell types that can assemble and mature in the form of human organs and tissues.

The tissues researchers generate from pluripotent stem cells can provide a unique source for personalized medicine from transplantation to novel drug discovery.

But unfortunately, synthetic tissues from stem cells are not always suitable for transplant or drug testing because they contain unwanted cells from other tissues, or lack the tissue maturity and a complete network of blood vessels necessary for bringing oxygen and nutrients needed to nurture an organ. That is why having a framework to assess whether these lab-grown cells and tissues are doing their job, and how to make them more like human organs, is critical.

Inspired by this challenge, I was determined to establish a synthetic biology method to read and write, or program, tissue development. I am trying to do this using the genetic language of stem cells, similar to what is used by nature to form human organs.

I am a researcher specializing in synthetic biology and biological engineering at the Pittsburgh Liver Research Center and McGowan Institute for Regenerative Medicine, where the goals are to use engineering approaches to analyze and build novel biological systems and solve human health problems. My lab combines synthetic biology and regenerative medicine in a new field that strives to replace, regrow or repair diseased organs or tissues.

I chose to focus on growing new human livers because this organ is vital for controlling most levels of chemicals like proteins or sugar in the blood. The liver also breaks down harmful chemicals and metabolizes many drugs in our body. But the liver tissue is also vulnerable and can be damaged and destroyed by many diseases, such as hepatitis or fatty liver disease. There is a shortage of donor organs, which limits liver transplantation.

To make synthetic organs and tissues, scientists need to be able to control stem cells so that they can form into different types of cells, such as liver cells and blood vessel cells. The goal is to mature these stem cells into miniorgans, or organoids, containing blood vessels and the correct adult cell types that would be found in a natural organ.

One way to orchestrate maturation of synthetic tissues is to determine the list of genes needed to induce a group of stem cells to grow, mature and evolve into a complete and functioning organ. To derive this list I worked with Patrick Cahan and Samira Kiani to first use computational analysis to identify genes involved in transforming a group of stem cells into a mature functioning liver. Then our team led by two of my students Jeremy Velazquez and Ryan LeGraw used genetic engineering to alter specific genes we had identified and used them to help build and mature human liver tissues from stem cells.

The tissue is grown from a layer of genetically engineered stem cells in a petri dish. The function of genetic programs together with nutrients is to orchestrate formation of liver organoids over the course of 15 to 17 days.

I and my colleagues first compared the active genes in fetal liver organoids we had grown in the lab with those in adult human livers using a computational analysis to get a list of genes needed for driving fetal liver organoids to mature into adult organs.

We then used genetic engineering to tweak genes and the resulting proteins that the stem cells needed to mature further toward an adult liver. In the course of about 17 days we generated tiny several millimeters in width but more mature liver tissues with a range of cells typically found in livers in the third trimester of human pregnancies.

Like a mature human liver, these synthetic livers were able to store, synthesize and metabolize nutrients. Though our lab-grown livers were small, we are hopeful that we can scale them up in the future. While they share many similar features with adult livers, they arent perfect and our team still has work to do. For example, we still need to improve the capacity of the liver tissue to metabolize a variety of drugs. We also need to make it safer and more efficacious for eventual application in humans.

[Deep knowledge, daily. Sign up for The Conversations newsletter.]

Our study demonstrates the ability of these lab livers to mature and develop a functional network of blood vessels in just two and a half weeks. We believe this approach can pave the path for the manufacture of other organs with vasculature via genetic programming.

The liver organoids provide several key features of an adult human liver such as production of key blood proteins and regulation of bile a chemical important for digestion of food.

When we implanted the lab-grown liver tissues into mice suffering from liver disease, it increased the life span. We named our organoids designer organoids, as they are generated via a genetic design.

Read the original post:
Genetic engineering transformed stem cells into working mini-livers that extended the life of mice with liver disease - The Conversation US

The lab of KrisSaha at the University of WisconsinMadison has developed an innovative combination of gene-editing tools and computational simulations that can be used to develop new strategies for editing genes associated with genetic disorders.

In proof-of-concept experiments, the labs researchers efficiently corrected multiple mutations responsible for a rare metabolic disorder, known as Pompe disease, in cells containing the disease-causing errors. They also used computer simulations to design the ideal gene-editing approach for treating human patients, a boon for rare disorders like Pompe disease that lack useful animal models.

Their promising platform advances the CRISPR genome-editing field and could lead to effective treatments for many diseases, not just Pompe disease.

The exact mutations seen in the Pompe patients are not in an existing animal model, so we cannot do all of the preclinical studies that we would like to do in order to evaluate the safety and efficacy of different genome editing strategies, says Saha, a professor of biomedical engineering at UWMadisons Wisconsin Institute for Discovery. We need a way to think about how we go from patient material to a therapy without having to build an animal model, a process that takes months to years and hundreds of thousands of dollars.

The lab of Kris Saha (standing) has developed an innovative combination of gene-editing tools and computational simulations that can be used to develop new strategies for editing genes associated with genetic disorders. Photo: Stephanie Precourt

Sahas team published its findings Dec. 8 in the journal Nature Communications.

In the first few months of life, an infant with Pompe disease becomes weaker and weaker as glycogen builds up in their muscles, their cells unable to break the complex sugar down. Multiple mutations in a gene calledGAAprevent their cells from correctly producing the proteins needed to make lysosomes, which turn glycogen into glucose, the fuel that powers cells. Left untreated, most patients with Pompe die within a year.

Developing effective therapies for such diseases can be difficult for a number of reasons. First, diseases like Pompe have no animal models in which to test treatments, a typical step in therapy development. And diseases like Pompe and many other inherited diseases are autosomal recessive, which means that mutations are present on both copies of a chromosome. Two sets of mutations require two successful gene-repair events for maximum effect. Further complicating the matter is the fact that many diseases are polygenic, resulting from mutations in two or more genes or multiple mutations spread across a single gene, as is the case for Pompe disease.

The Saha labs new approach uses precise gene-editing tools to edit both faulty alleles simultaneously within individual cells to restore function. In its new report, the research team used induced pluripotent stem cells derived from Pompe patients to reproduce the exactGAAmutations that cause the disease and to approximate the resulting tissue pathology.

To fix these Pompe mutations, the lab turned to a specially designed, ultra-precise genome-editing system described in aprevious studyled by Jared Carlson-Stevermer, who was at the time a graduate student in Sahas group. That report established an up to 18-fold increase in precision of gene edits by combining a DNA repair template with the cutting machinery of CRISPR in one particle.

In the current study, the researchers used the method to fix two mutations at once in Pompe-derived cells. By doing so, the researchers improved cell function dramatically, bringing lysosome protein production up to the level of healthy cells without any major adverse effects, which sometimes emerge from gene editing.

The research advances the CRISPR genome-editing field and could lead to effective treatments for many diseases.

But treating cells in the laboratory, while providing crucial insight, is not the same as creating a therapy for patients. A critical step in developing treatments usually involves testing on animal models to evaluate efficacy and safety, a major obstacle for Pompe disease and other genetic conditions that lack viable animal models.

To determine the best therapeutic strategy for polygenic diseases evaluating different doses, delivery mechanisms and timing, risks and other factors the research team instead built a computational model that allows it to predict the outcomes of various conditions.

This allows us to survey a wider scope of many different gene therapies during the design of a strategy, says coauthor Amritava Das, a postdoctoral associate at the Morgridge Institute for Research. The computational approach is critical when you dont have an animal model that resembles the human disease.

After pumping close to a million simulation conditions through the computational model, Das, Carlson-Stevermer and Saha have gained key insights about the delivery of gene editors into the livers of human infants with Pompe disease without having to subject a single patient to experimental treatments. And those insights establish that the multiple-correction genome-editing approach tested in stem cells may be an effective treatment for Pompe and other polygenic recessive disorders.

The computational model, which can be easily adapted for other polygenic conditions, is a big step for the development of therapies for diseases like Pompe and lays the groundwork for a bridge from laboratory studies to the clinic. And as more measurements are added to the model, it will gain more predictive power.

Its a very broad, adaptable platform, Das says about the combined stem cell model and computational tool, and a very different way of thinking about gene therapy.

This work was supported by the National Science Foundation (CBET-1350178, CBET-1645123), the National Institutes of Health (1R35GM119644-01), the Environmental Protection Agency (EPA-G2013 STAR-L1), the University of Wisconsin Carbone Cancer Center (P30 CA014520), the Wisconsin Alumni Research Foundation, and the Wisconsin Institute for Discovery.

Read the rest here:
Multiple gene edits and computer simulations could help treat rare genetic diseases - University of Wisconsin-Madison

Heres how the mechanism works: Humans alone observe the world and ask questions that demand why, how and what. They answer their questions by looking for if-and-then patterns, such as, if I boil an egg for eight minutes, then the yolk will be hard, and if I boil an egg for four minutes, then the yolk will be soft. They use those patterns to build theories, which they then repeatedly test, looking always for systems to further employ and exploit.

Grand theories aside, Baron-Cohen is at his most striking when he writes about people with autism, like Jonah, who was slow to talk but who taught himself to read. When Jonah eventually learned to speak, he used language less as a tool for communication than as a system for categorizing the world around him. As a young child, he was endlessly fascinated by how things worked, and he spent hours experimenting, like flipping a light switch on and off to test and retest its effect. At school he showed great brilliance in his observations about the natural world, he was a born pattern seeker, but at the same time he was taunted by other children for being so different. In group reading time, which he hated, he would shut his eyes and put his fingers in his ears. Jonahs weekend hobby as a young man was helping fishermen locate shoals by being able to read the signs from surface waves. Yet despite his incredible talents, Jonah was lonely and frustrated because he couldnt find a job that would allow him to live an independent life. Baron-Cohen argues with feeling and conviction that society must do a better job of making room for people like Jonah, and that it will benefit enormously when it does.

Mostly, though, The Pattern Seekers is about the idea of using autism as a key to unlock the mystery of human cognition, and on this front, its less convincing. Sometimes its simply because the books framing is misleading. Baron-Cohen takes great care to set up the idea that all humans possess a Systemizing Mechanism, that some people are hyper-systemizers, and that a comparatively high number of those hyper-systemizers are autistic. But the subtitle of the book is not how systemizing drives human invention, its how autism drives human invention. At the same time, he cautions against speculation that people, living or dead, might be autistic. The term should be reserved only for diagnosis when people are struggling to function, he explains.

In addition, Baron-Cohen divides humans into five brain types, grouping people who are more or less likely to systemize or empathize. He believes that humans also uniquely possess an Empathy Circuit. But he establishes his five groups by conducting large surveys about individual tendencies and traits, so they are not brain types at all. They are, at best, mind types.

Read more here:
Does Autism Hold the Key to What Makes Humans Special? - The New York Times

SOUTH SAN FRANCISCO, Calif. & LEXINGTON, Mass.--(BUSINESS WIRE)--Maze Therapeutics, a company focused on translating genetic insights into new medicines, and Alloy Therapeutics, a company developing platforms and services to enable drug discovery, today announced the formation of Broadwing Bio to develop targeted antibody therapies for the treatment of ophthalmic diseases. Broadwing Bio will advance programs directed to genetically validated ophthalmology targets identified using Mazes human genetics and functional genomics platform, the COMPASS platform. Alloy Discovery Services will generate therapeutic candidates using Alloys broad suite of antibody discovery technologies, including the ATX-Gx mouse platform.

Under the terms of the agreement, Maze and Alloy will fund Broadwing Bio to rapidly advance its programs through preclinical and clinical development with the opportunity for independent financing and partnering. Maze and Alloy will retain certain rights to participate in the development and commercialization of products originating from Broadwing Bio. The company will be led by Andrew Peterson, Ph.D., founder and chief executive officer of Broadwing Bio.

We are very excited to partner with Alloy on the formation of Broadwing Bio, with a mission to advance therapeutics for ophthalmology indications, said Jason Coloma, Ph.D., chief executive officer of Maze. Maze is advancing a pipeline of programs based on genetic insights of disease, without restrictions on modality or therapeutic area. This joint venture will allow us to pursue compelling Maze-identified targets through a dedicated organization with the experience and focus to develop highly differentiated therapies addressing unmet needs in ophthalmology, while retaining significant financial participation and product rights.

Broadwing Bio is a great example of the high impact partnerships Alloy Discovery Services will conduct on a very select basis, where we can invest heavily in the success of the partnership, said Errik Anderson, chief executive officer and founder of Alloy Therapeutics. We are honored to be working with an incredible scientist-entrepreneur like Andy, in partnership with Mazes team, to advance these exciting drug targets designated by Maze.

Broadwing Bio has established a team of experienced leaders and scientific advisors, including

There are a number of ophthalmic diseases for which effective therapeutic options are limited, but recent genetic insights provide avenues to change this situation, said Dr. Peterson. Broadwing Bio has the very unique opportunity to bring together the capabilities of two exceptional companies in order to develop novel treatments targeted at these diseases. Im thrilled to join the company as CEO and look forward to building the Broadwing Bio team, while leveraging Maze and Alloys insights and experience in drug discovery in order to bring medicines to patients in need.

About Maze Therapeutics

Maze Therapeutics is a biopharmaceutical company developing a broad portfolio of therapeutic candidates for a number of genetically defined diseases. Maze is focused on translating genetic insights into new medicines by utilizing an approach that combines the analysis of large-scale human genetics data, cutting-edge functional genomics and an array of drug discovery approaches. The Maze COMPASS platform reveals modifier genes that confer protection and provides deeper understanding of the target biology and how these targets can be best targeted with drug therapies. Maze was launched in 2019 by Third Rock Ventures, with funding from ARCH Venture Partners, GV, Foresite Capital, Casdin Capital, Alexandria Venture Investments, City Hill and other undisclosed investors. Maze is based in South San Francisco. For more information please visit mazetx.com.

About Alloy Therapeutics

Alloy Therapeutics is a biotechnology company dedicated to empowering scientists in the relentless pursuit of making better medicines for all. To this end, Alloy seeks to democratize access to foundational drug discovery platforms and services to scientists worldwide. Alloys first platform, the ATX-Gx mouse platform, is a suite of transgenic mice designed for best-in-class in vivo discovery of fully human monoclonal antibodies. Alloys partners include academic scientists, small and medium biotech, and Fortune 50 biopharma. Founded in 2018 and privately funded by visionary investors, Alloy Therapeutics is headquartered in Boston, Massachusetts with European labs in Cambridge, UK. As a reflection of our irrational commitment to the scientific community, 100% of our revenue from platforms and services is reinvested in innovation and supporting access to innovation. To join the revolution, visit alloytx.com or schedule a 15-minute chat with our Founder and CEO at alloytx.com/ceo.

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Maze Therapeutics and Alloy Therapeutics Form Broadwing Bio to Develop Antibody Therapies for Genetically Validated Targets in Ophthalmic Diseases -...

Researchers at the University of Pittsburgh School of Medicine have combined synthetic biology with a machine-learning algorithm to create human liver organoids with blood- and bile-handling systems. When implanted into mice with failing livers, the lab-grown replacement livers extended life.

The study, published today in Cell Systems, shows that its possible to trigger and speed up the maturation of a lab-grown organ without sacrificing precision or control.

Mo Ebrahimkhani lab featurePregnancy is nine monthsit takes that long and even months after birth for new organs to maturebut if a person needs a liver, they may not be able to wait that long, said study author Mo Ebrahimkhani, M.D., associate professor of pathology and bioengineering, and member of the Pittsburgh Liver Research Center and the McGowan Institute for Regenerative Medicine. We showed its possible to get human liver tissue with four main cell types and vasculature in 17 days. We can mature tissue almost to the third trimester in only three months.

Other groups have attempted to coax organoid maturation in a dish using growth factors, but its expensive, inconsistent and prone to human error, Ebrahimkhani said. Often, there are unwanted tissue or cell typessuch as intestine or brain cells growing in the middle of what should be solid liver.

Using genetic engineering is cleaner but also more complex to orchestrate. So, Ebrahimkhani partnered with Patrick Cahan, Ph.D., at Johns Hopkins University to use a machine-learning system that can reverse engineer the genes necessary for human liver maturation.

Ebrahimkhani Vasculature releaseThen, Ebrahimkhani together with his collaborator at Pitt, Samira Kiani, M.D., applied genetic engineering techniques, including CRISPR, to turn a mass of immature liver tissueoriginally derived from human stem cellsinto what the team calls designer liver organoids.

The more mature the organoids got, the more capillaries and rudimentary bile duct cells snaked their way through the thin sheet of tissue, and the more closely the function of the tiny organ rivaled its full-size natural human model. Energy storage, fat accumulation, chemical transport, enzyme activity and protein production were all closer to adult human liver function, though still not a perfect match.

Ebrahimkhani imagines designer organoids having three main uses: drug discovery, disease modeling and organ transplant. Since the stem cells can come from the patients own body, lab-grown organs could be personalized, so there would be no threat of immune rejection.

When transplanted into mice with damaged livers, Ebrahimkhanis designer liver organoids successfully integrated into the animals bodies and continued to workproducing human proteins that showed up in the animals blood and prolonging the animals lives.

This is a proof-of-principle to show that its possible, Ebrahimkhani said. The technique could potentially go much further.

Our reference was a nature-designed human liver, but you can go after any design you like. For instance, you can make a genetic switch that protects the tissue from a virus, target the DNA of the virus and destroy it, Ebrahimkhani said. That sets this method apart.

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Synthetic Biology Speeds the Creation of Lab-Grown Livers - India Education Diary

LOGAN Genetically engineered golden Syrian hamsters developed by Utah State University researchers played a key role in animal trials of a possible vaccine to protect against the virus that causes COVID-19.

The Rega Institute in Leuven, Belgium, has used the hamsters produced by professor Zhongde Wang and his lab at USU to test the safety and effectiveness of a possible vaccine.

Details of the research conducted by the Rega Institute and its findings were published online in the journal Nature this week.

The candidate vaccine was found to be safe and effective in several animal models by a team of scientists at the institute.

Animal models play a vital role in vaccine research "because we cannot directly test them in humans. We need to use animal models, (it's) very critical," Wang said.

Wang said two pairs of hamsters were shipped to the Belgium lab in 2018 to start a breeding colony in an agreement with his lab.

"The scientists in my lab and I are very gratified that our research is contributing to combating this raging COVID-19 pandemic," Wang said in a statement.

"We also feel grateful for the excellent support from USU's Laboratory Animal Research Center to help us to carry out the research."

The Wang lab, established at USU in 2012, developed the first genetic hamster models in the world. The models are used in more than a dozen labs and institutions including the National Institutes of Health, the U.S. Army Medical Research Institute of Infectious Diseases, and Public Health Agency of Canada.

Hamsters from Wang's lab are also utilized in COVID-19 and other studies in USU's Institute for Antiviral Research.

"We pioneered development of genetic engineering techniques in this species and now we have about 30 different models. These are 30 different genetic modifications," Wang said in an interview Wednesday,

Typically, rodents carry many disease-causing organisms without becoming sick. The USU lab genetically engineered the golden Syrian hamsters to be susceptible to viruses that infect humans.

Viruses frequently attach to receptors in humans that are not present in animals, which limits effective testing of potential drugs to prevent or treat diseases. Hamsters from Wang's lab have a human gene inserted into their DNA for the receptor to which this coronavirus binds to facilitate testing, according to a university press release.

Because the hamsters are designed specifically to react to disease challenges more like humans, it takes fewer experiments to verify results, which expedites the process and can reduce numbers of animals used in research.

"We take animal welfare extremely seriously, and only the minimum numbers of animals required are used," said Wang, a professor in the Department of Animal, Dairy and Veterinary Sciences, in an article posted on a university website.

"In addition to that, all procedures are approved by Institutional Animal Care and Use Committees. It is essential to use these animals in vaccine studies before trials can be done in human subjects."

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Hamsters genetically engineered by USU researchers are on the front lines of COVID-19 vaccine trials in Belgium - KSL.com

However, in both medicine and dentistry, there is an important role as well for ingenious, low-tech, less expensive approaches to improved health and increased longevity.

The FDA last year approved a high-tech gene therapy drug, Zolgensma, for a rare childhood genetic disease, spinal muscular atrophy, that costs justover $2 millionfor the single dose of the treatment.The illness, which is caused by a defect in a gene calledSMN1, affects about 400 babies in the United States annually and kills those with the most common form of the disease in the first few years of life.The new treatment uses non-pathogenic, genetically engineered viruses to deliver healthy copies of theSMN1gene to patients cells so they can synthesize a protein needed to develop normal muscle neurons.

Another remarkable genetic engineering feat wasreportedin the journalNaturein 2017.An experimental gene therapy procedureused to transform and grow sheets of healthy skin saved the life of a 7-year-old boywho suffered from a genetic disease,junctional epidermolysis bullosa, that had blistered and destroyed most of his skin.He was on the verge of death, but two years after the treatment with genetically engineered cells produced by a multi-national team, he had healthy skin and was leading a normal life.

Those high-tech interventions are spectacular, but there are many simpler and cheaper yet tremendously important innovations for the diagnosis and prevention of illness.Among the most cost-effective are checklists for personnel in operating rooms and ICUs. According to a Norwegian research group, Safety checklists appear to be effective tools for improving patient safety in various clinical settings by strengthening compliance with guidelines, improving human factors, reducing the incidence of adverse events, and decreasing mortality and morbidity.

Sometimes, a simple tool or device is important to clinical diagnosis. One example is the hand-held direct ophthalmoscope, which allows a medical practitioner to look intotheback oftheeye to ascertain the health oftheretina, optic nerve, vasculature, and vitreous humor (the liquid inside the eyeball). Invented in 1851, it costs less than $200.

Another example is the way a singleblood testcan ascertain that a patient in the emergency room is not having a heart attack and so can forego the inconvenience and expense of additional invasive tests or unnecessary hospitalization.The highly sensitive blood test measures levels of cardiac troponin, a protein involved in muscle contraction; if the level is undetectable that is, below the limit of detection of the test there is a greater than 99% likelihood that the patient isnotexperiencing a heart attack and is at very low risk of other cardiac adverse events for at least 30 days.

That innovative approach is advantageous to patients and helps to reduce the frequency of hospitalizations and, therefore, healthcare costs.

Falls are both a cause and effect of declining health in the elderly.They are the leading cause of injury-related visits to emergency rooms and the primary cause of accidental deaths in Americans over the age of 65.To measure the potential benefits of a low-tech approach to preventing injuries from them, a research group in New Zealandcompared rates of falling and injuriesfrom falls on low-impact flooring (LIF) compared with standard vinyl flooring on an older persons health ward.Falls were prospectively monitored with written reports of all incidents, noting the location and consequences of each fall.The frequency of falls and injuries on LIF and those occurring on standard vinyl flooring (controls) were compared.

The investigators found that over the 31months of the study, there were 278 falls (among 178 persons who fell).The rate of falls was indistinguishable in the two groups, but fall-related injuries were significantly less frequent when they occurred on LIFs (22% of falls versus 34% of falls on control flooring).And many of the injuries that were averted were serious: Fractures occurred in 0.7% of falls in the LIF cohort versus 2.3% in the control cohort.

Thus, the New Zealand study provides a compelling rationale for adding low-impact flooring to housing for seniors (along withother modifications).

Dentistry has also benefited from costly high-tech innovations such asdental implants, but low-tech prophylaxis can also provide much needed benefits for dental health.

Tooth decay remains one of the majorpublic health concerns for both developing and developed countriesaccording to the World Health Organization.It is one of the most commonchronic problemsin the United States, where most adults will have at least one cavity in their lifetime. Decay causes inflammation in surrounding gum tissue, abscesses, and eventually, tooth loss. In addition to taking a significant toll on quality of life, decay and periodontitis has been linked to an increased risk of cardiovascular events, systemic infections such as endocarditis, and complications in pregnancy.

There have been significant advances in replacing and restoring teeth that need treatment due to dental caries, and these are often costly. However, preventing the problem in the first place is optimal, and an important advance was the introduction of water fluoridation, a simple low-tech intervention withproven efficacy, in 1945. The concept is that fluoride, a negatively charged ion, binds to calcium and phosphate on tooth surfaces to prevent the bacteria that cause cavities from even entering the tooth, thus protecting the teeth from dental decay and in some cases even reversing early decay. In a systematic review published in 2016, researchersfoundthat fluoridating drinking water in communities decreased overall decay and, thereby, the cost of more aggressive and costly dental interventions.

The Centers for Disease Control estimates that there are approximately100 million Americanswho are still without access to fluoridated water. Introducing this low-tech, high-impact measure more widely would substantially decrease the need for many dental procedures.

The high-tech miracles will continue to garner headlines, but to advance public health, simpler and relatively inexpensive innovations are also essential. That has policy implications: We need to put research dollars not only into potential big-ticket, high-tech blockbusters but also into ingenious, low-tech innovation.

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High-tech medical and dental innovation garner the headlines but the most impactful practices are mostly lower tech and prevention-focused - Genetic...