Daily Archives: August 13, 2017

Like a fast-growing child constantly outgrowing clothes, biotech giant Illumina has trouble keeping up with its continued expansion.

So on Monday, the San Diego genome sequencing leader is scheduled to open a new addition a 7-acre, 316,000 square-foot complex called the i3 campus. Illumina considers it an extension of its headquarters, less than a mile away in the University Town Center area.

Consisting of three buildings refitted for Illuminas needs, the i3 campus emphasizes openness, with ample windows to the outside and an open-style office space inside. Amenities include a gym and a restaurant called Salt + Air.

And there are meeting rooms lots of meeting rooms. Larger rooms, for formal presentations, can be reserved. Smaller ones, where one or two people can sit, are available on the fly for the innumerable spontaneous discussions that seem to be baked into Illuminas DNA.

Employees manage their own day and calendars, so we infused the i3 workplace with open and non-bookable places for employees to work these can be visitors from the main HQ campus or employees from another site, said Jenny Durbin, the companys global facilities manager. An employee can choose to work at i3 even if their team or department is based at the main campus.

Illumina employs almost 7,000 people, nearly 3,000 of them in San Diego. Its stock is valued at more than $28 billion, making it by far the highest valued biotech in San Diego.

In January 2014, Illumina made international headlines by bringing down the cost of sequencing a human genome to below $1,000, with its HiSeq X Ten Sequencing System. And this January, the company announced machines in its NovaSeq line that can reduce the time to process a human genome to an average rate of one per hour, when many are processed in large batches.

As a result of such advances, Illumina dominates the market for DNA sequencers. It also leverages genomic technology into such fields as prenatal testing.

Since its impossible to know what scientific research will lead to new opportunities, Illumina makes sure its employees have flexibility, Durbin said. As biomedical research unveils new breakthroughs, Illumina races to translate the research into new products to serve the field, in government, academic and medical applications.

The i3 campus was developed by BioMed Realty, designed by the Seattle architectural firm of Perkins + Will, and built by McCarthy contractors. Tucked onto seven acres at the east end of Executive Drive, its cantilevered buildings perched like hawks over Interstate 805.

Theres a common theme working up and down the coast, said design principal Ryan Bussard, looking for innovation in architecture, tying together site design as well as architecture and collaboration spaces. The indoor and outdoor down here you can really take advantage of that year-round. Its pretty unique.

BioMed Realty held a design competition in 2011 that Perkins + Will won, five years before Illumina signed a lease for the property, and the architects and developers had to conceive a building before the users needs were known.

One of the first decisions was to demolish a never-occupied building and locate parking underground to gain more above-ground usable space.

The siting of the building was kind of a invert of the traditional, Bussard said.

That cost more but yielded highly valued space, including a 33,500-square-foot courtyard.

The second decision was to build three concrete-and-glass buildings and cantilever them out toward I-805 as much as 30 feet beyond the lower floors. The effect is to float above the landscaped fire lane where the company will host its first big event next month.

Its almost weightless, he said.

The local inspirations? The Salk Institute and the J. Craig Venter Institute on Torrey Pines Mesa. About 40,000 cubic yards of smooth white concrete make up the structure, rather than a more traditional steel-and-glass framework.

That eliminated the need to locate elevators, bathrooms and other core facilities in the middle of the buildings and increased the flexibility of each floors layout.

The third decision was to set aside half the building to be used for lab space on the interiors and administrative space around the exterior walls. But Illumina chose to make the entire building into office space a shift that could be reversed in the future.

We build flexible space for the infrastructure to support, Bussard said.

Inside the three buildings, the finance, marketing and other company executives will work to turn researchers inventions and findings into products and services.

Perkins + Will designers took the companys philosophy of work anywhere and created interior design layouts that decouple staff from their desktop phones, computers and potted plants.

Large and small meetings will be scheduled in a variety of ground-floor spaces in Building B, located to the right of the campus entrance. One conference room can be extended to about 120 feet in length and voice-sensitive cameras can transmit the proceedings off campus.

A smaller plaza lounge at the end of the building offers a more informal space in a midcentury modern, 60s residential look. Durbin, the global facilities manager, called the approach resimercial a mashup of residential and commercial design.

Its a blend between formal spaces and a more home-like space, she said.

To orient employees no matter where they work, the same colors are being used floor by floor the first floor is pumpkin orange, the second is blue and the third green. Abstract carpet patterns complement the color scheme.

Its important to have innovation and consistency, said Norm Fjeldheim, senior vice president, chief information officer and head of global facilities.

Some employees will have assigned desks that can be adjusted for standing or sitting, while others can move day to day, depending the task at hand. At night they can store their personal items in lockers. For private phone conversations, there are 60 phone booths in the complex but bring your own cell phone that links into the buildings WiFi network.

Those desks and phone booths will be used by people not only from San Diego, but from around the world.

Besides San Diego, Illumina has offices in Hayward, Santa Clara, San Francisco, Redwood City, Madison, Wis.; and internationally in Victoria, Australia; Shangai and Beijing; Tokyo; So Paulo; Eindhoven, the Netherlands; Chesterford and Fulbourn, United Kingdom; Singapore; and Victoria, Canada.

As a company with a worldwide presence, Illumina uses technology to bridge the gap between its widespread locations, said Durbin said.

I feel as an employee working across the globe that my team members and colleagues at the other sites feel just as close to me as my team mates here, because we make the efforts to use the technology (Jabber, message, box, video and teleconferencing) to bridge the distance, Durbin said.

In San Diego, Illuminas presence goes far beyond its direct employment. Local biomedical institutions such as Scripps Health, the J. Craig Venter Institute and Rady Childrens Hospital San Diego are Illumina customers. Illumina is also a longtime charitable supporter of Rady Childrens.

When babies show up at the hospital with unidentifiable serious illnesses, their genomes may be sequenced with Illumina products to find clues to their condition. This can save lives and prevent unneeded procedures.

Shimul Chowdhury, Rady Childrens clinical laboratory director, used to work for Illumina. As a board-certified molecular geneticist, he analyzes the genetic data from clinical reports and delivers them to physicians.

My role as a laboratory director is really to be the bridge between the laboratory who presents the reports to our physicians in a manner that they understand and that is useful for them to be able to take care of their patients, Chowdhury said.

At Illumina, he worked in the clinical laboratory, seeking to learn what information could be gleaned from a genome to make genome sequencing become routine in clinical practice. That required him to analyze patient samples and collaborate with doctors. He collaborated with Dr. Stephen Kingsmore, who heads the Rady Institute for Genomic Medicine.

As Chowdhury learned more about Rady Childrens, he decided to join the hospital to help put genomic technology into clinical practice. And his work still very much involves technology from Illumina.

Theyre providing the instruments and the reagents (supplies) to help us sequence kids, Chowdhury said. But it goes broader than that in terms of collaboration. Were taking these sequencing technologies and testing them in patients in intensive care units. So I think our feedback is valuable to them.

On a larger scale, he said Illuminas presence in San Diego draws visibility to use of the technology.

It really increases the genomics literacy of this region, which really helps us when were speaking to families, speaking to doctors, he said.

Radys uses Illuminas most advanced genomics instrument, the NovaSeq, Chowdhury said. With speed and accuracy, the instrument is important for searching for genetic causes of disease in children who may be critically ill and not have much time left.

We really view this machine as a next step in our evolution for being able to provide rapid genomes for more and more kids in San Diego and throughout the United States, he said.

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Cameron's visit to Illumina continues San Diego's British biotech invasion

Illumina CEO brings entrepreneurial spirit to genomics giant

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Illumina helps doctors diagnose sick babies faster

bradley.fikes@sduniontribune.com

(619) 293-1020

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Genome leader Illumina expands again in San Diego - The San Diego Union-Tribune

What is it?

In a first, researchers from the Oregon Health and Science University along with colleagues in California, China and South Korea repaired a mutation in human embryos by using a gene-editing tool called CRISPR-Cas9.

The mutation seen in the MYBPC3 gene causes a common heart condition called hypertrophic cardiomyopathy, which is marked by thickening of the heart muscle.

The mutation is seen in about one in 500 people and can lead to sudden death later in life. It is an inherited cardiac disease and the presence of even one copy of the gene can cause symptoms, which usually manifest as heart failure. Correcting the mutation in the embryo ensures that the child is born healthy and the defective gene is not passed on to future generations. There is currently no cure for the condition.

How did it come about?

CRISPR-Cas9 is a system used by bacterial cells to recognise and destroy viral DNA as a form of adaptive immunity. Using components of the CRISPR system, researchers can remove, add or alter specific DNA sequences in the genome of higher organisms.

The gene editing tool has two components a single-guide RNA (sgRNA) that contains a sequence that can bind to DNA, and the Cas9 enzyme which acts as a molecular scissor that can cleave DNA. The genetic sequence of the sgRNA matches the target sequence of the DNA that has to be edited. In order to selectively edit a desired sequence in DNA, the sgRNA is designed to find and bind to the target.

Upon finding its target, the Cas9 enzyme swings into an active form that cuts both strands of the target DNA. One of the two main DNA-repair pathways in the cell then gets activated to repair the double-stranded breaks. While one of the repair mechanisms result in changes to the DNA sequence, the other is more suitable for introducing specific sequences to enable tailored repair. In theory, the guide RNA will only bind to the target sequence and no other regions of the genome.

But the CRISPR-Cas9 system can also recognise and cleave different regions of the genome than the one that was intended to be edited. These off-target changes are very likely to take place when the gene-editing tool binds to DNA sequences that are very similar to the target one. Though many studies have found few unwanted changes suggesting that the tool is probably safe, researchers are working on safer alternatives.

Why does it matter?

Along with sperm from a man with hypertrophic cardiomyopathy, the gene-editing tool was also introduced into eggs from 12 healthy women before fertilisation. In normal conditions, a piece of DNA with the correct sequence serves as a template for the repair to work, although the efficiency can be significantly low. Instead of the repair template that was provided by the researchers, the cells used the healthy copy of the DNA from the egg as a template. This came as a big surprise.

Normally, if sperm from a father with one mutant copy of the gene is fertilized in vitro with normal eggs, 50% of the embryos would inherit the condition. When the gene-editing tool was used, 42 out of the 58 embryos did not carry the mutation. The remaining 16 embryos had unwanted additions or deletions of DNA.

Thus the probability of inheriting the healthy gene increased from 50 to 72.4%. There was no off-target snipping of the DNA. According to Nature, the edited embryos developed similarly to the control embryos, with 50% reaching an early stage of development (blastocyst). This indicates that editing does not block development.

What next?

Clinical trials are under way in China and in the U.S. to use this tool for treating cancer. In May this year, it was shown in mice that it is possible to shut down HIV-1 replication and even eliminate the virus from infected cells. In agriculture, a new breed of crops that are gene-edited will become commercially available in a few years. In February this year, the National Academy of Sciences (NAS) and the National Academy of Medicine said scientific advances make gene editing in human reproductive cells a realistic possibility that deserves serious consideration.

Original post:
What is genome editing? - The Hindu

Using the genome-editing technology CRISPR, scientists deactivated a family of retroviruses within the pig genome overcoming a large hurdle in the path to the transplant of pig organs into humans.

Transplantation from one species to another -- xenotransplantation -- holds "great promise," the American and Chinese research team believes.

Retroviruses carry their genetic blueprint in the form of ribonucleic acid (or RNA) and transcribe this into deoxyribonucleic acid, commonly known as DNA. This is a reverse of the usual transcription process, which flows from DNA to RNA. This reversal makes it possible for retrovirus genes not only to infect cells but to become permanently incorporated into a cell's genome.

In particular, the pig genome is known to carry porcine endogenous retroviruses (or PERVs), which are capable of transmitting diseases, including cancers, into humans. The presence of these PERVs means pig organs cannot now be safely transplanted into humans.

But George Church of MIT's Broad Institute and Harvard, Dong Niu of Zhejiang University and their colleagues demonstrated a new method for deactivating the retroviruses in a pig cell line as a way to eliminate the transfer of PERVs to human cells.

First, the researchers proved that PERVs can be transmitted from pig to human cells and transmitted among human cells, even in conditions in which the fresh human cells have no prior exposure to pig cells.

Next, the team created a map of the PERVs in the genome of pig fibroblast (connective tissue) cells. Having identified a total of 25 PERVs, the science team used CRISPR to edit out -- or deactivate -- all those gene sites.

The scientists grew clone cells of these edited cells but were unable to cultivate one with greater than 90% of the PERVs deleted. But they added "ingredients" during the gene modification process -- including both growth factors and growth inhibitors -- and finally succeeded.

The new cells had 100% of the PERVs deactivated.

From here, the researchers produced PERV-inactivated embryos and implanted them into sows. The resulting piglets exhibited no signs of PERVs.

Dr. Ian McConnell, emeritus professor of veterinary science at the University of Cambridge, sees the research as a "promising first step." McConnell, who was not involved in the study, added that "it remains to be seen whether these results can be translated into a fully safe strategy in organ transplantation."

Formidable obstacles remain "in overcoming immunological rejection and physiological incompatibility of pig organs in humans," he said.

Scientists have been introducing human cells into animals to create models of diseases for decades, yet the 2009 policy suspended funding for chimera-based research due to ethical concerns.

With the advance of both stem cell and gene editing technologies, the ability to create more sophisticated animal-human chimeras raised concerns. Worries include human cells populating the brain of an animal thus humanizing that animal. Alternatively, human cells populating the germline of an animal could enable human genes to pass onto offspring.

The National Institutes of Health hopes a revised policy will enable research to continue -- safely.

The new research supports the value of using CRISPR to deactivate PERVs and so brings pig organs one step closer to safe transplantation, concluded the scientists.

Though more research is needed, they believe the "PERV-inactivated pig" can serve as a foundation strain that might be further engineered to "provide safe and effective organ and tissue resources" for transplantation into humans.

Read the original here:
Scientists edit pig genome with goal of human organ transplants - CNN

In a collaborative effort across a number of institutions, including Harvard, the Dana-Farber Cancer Institute, and the Broad Institute of MIT, researchers have narrowed down 760 genes directly responsible for the survival of cancer cells.

Although most of the vulnerable genes vary from one cancer type to another, around 10 percent are consistent between types, making them possible targets for cancer-fighting therapies.

The study, published in the journal Cell, utilized small interfering RNA, or siRNA, to turn off single lines of DNA and see which cells were affected. Overall, 17,000 genes were tested in over 20 different kinds of cancer.

Even though so many genes were studied, 90 percent of the cancers tested only vitally relied on 76 sets of genes, indicating that many other cancers may also have a small core of key genes that can be exploited as treatment targets.

Additionally, a scientist used biomarkers to divide cells into groups that describe their role in biology with over 400 of the 769 mapped genes.The groups account for roles such as gene mutation, reduced or increased gene expression, and gene function.

Through the study, it was discovered that 20 percent of the vital genes were already targeted for existing drug therapies, providing more proof of their efficacy.

While the full cancer genome hasnt been identified for all types, the work is well under way, meaning doctors and scientists have more information with which to battle cancer and help patients with better treatments.

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Early Version of Cancer Genome Reveals Vital Vulnerabilities - TrendinTech