Category Archives: Transhuman News

Oxford Genetics founder and CEO Ryan Cawood told me about his companys improvements to DNA design for better biologicals.

Last month at Synbiobeta, I caught up with Ryan Cawood, who created one of the most successful synthetic biology companies around, Oxford Genetics. Our direction actually took off from this conference, he told me. We saw that the cost of DNA synthesis is going to be driven down, so this was not a market for us to compete in.

Instead of focusing on making DNA engineering cheaper, Cawood decided to explore how to improve the quality of its products. Specific inspiration came in the form of frustration as he was trying to finish his PhD in genetics at Oxford University

I was making gene therapy plasmids, and they were increasingly hard to test because we just couldnt make them. They were 50 to 100 kilobases for different viruses with no standardization one section camefrom Spain, one section from the US, and one from the back of the freezerit was a sort of genetic car crash, as my PI, Len Seymour, called it.

As a company, we set out to improve this by focusing on DNA design we now help other companies working on therapeutics develop them better with SnapFast, a lego-like core DNA system.

In 2011, I formed the company by taking out bank loan. Then I negotiated a lab bench from local company in return for gene engineering for them. Finally, I built a website. Ive since obtained seven grants and connected with solid investors. Mercia Technologies has invested three times now the first time was in 2013 and on this next round, someone else will probably come in as well.

Len, my former lab PI, is still on the board as one of the cofounders. He was actually involved in founding two biotech companies before hand, one for oncolytic viruses (PsiOxus Therapeutics) and one for protein expression (The Native Antigen Company).

Cawoods lightning talk at Synbiobeta: fromsynthetic biology, Oxford Genetics is building up to improve biological drugsto reachpersonalised versions.

Well, our trajectory and plan was to build better DNA tech for the design and synthesis to discover and manufacture biologicals better. Fundamentally, youre always trying to build a tool to develop these better.

What Id like to see from the field is a major advancement of human therapeutics. There are four major challenges in biological development that were working to address: discovery, design, production and delivery basically every step.

We think Snapfast DNA will improve all of them because DNA is an integral part of each. So, we can absolutely use synbio to improve cell and gene therapies and biologics.

People who work in the area think of synbio as making things in algae, or making new genetic circuits etc, but dont necessarily see consequences for human health. The field has a huge role to play in tying the genetics of an individual human to a therapeutic treatment based on DNA. At the moment, there is no such pairing were a long way from that, but with synbio well get there.

We take a sort of blunt hammer approach now: its very inefficient therapeutically, and its a very inefficient use of government funds. By funding a better understanding of people, youll see significant gains intreatmentefficiencies.

The current approach is far too retrospective at the moment: we give a drug and then try to figure out why it worked in some people afterwards, or we just carry on giving it everyone knowing only a few people will benefit, in the future I hope we can predict efficacy and act upon that calculation.

Im still very much motivated by the therapeutic side of synthetic biology. Not everyone working at the company has a background in human genetics some come from working on archaea, but they all are oriented towards working towards therapeutics. Even my PA has first class degree in genetics.

DNA foundries are all the rage in synbio now, but we were much more interested in biology than physical manufacture that is, were much more focused on end goal versus how you get there. This thinking has changed the company a lot: instead of just making things, were designing things.

Images from Oxford Genetics,author at Synbiobeta, 04 April 2017, Mercia, & Sergei Drozd, Saibarakova Ilona /shutterstock.com

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This Founder is using Synbio to Revolutionize Genetic Medicine - Labiotech.eu (blog)

May 1, 2017 Credit: Vera Kratochvil/public domain

Researchers have found a genetic explanation for how smoking can lead to coronary heart disease (CHD). Many people have a protective gene type that reduces levels of an enzyme connected to artery-clogging fatty plaques and CHD. However, in people carrying this gene, smoking counteracts the protective effect.

"Our finding suggest that interventions to inhibit this enzyme would be particularly beneficial for smokers, and they may also prove useful for anyone at heightened risk of coronary heart disease," said study leader Muredach P. Reilly, MBBCH, MSCE, the Herbert and Florence Irving Professor of Medicine (in Cardiology) and director of the Irving Institute for Clinical and Translational Research at Columbia University Medical Center (CUMC).

The study, the largest of its kind, was published online today in the journal Circulation.

Cigarette smoking is known to cause about one in five cases of CHD, and is linked to approximately 1.6 million deaths worldwide each year. But the precise mechanisms by which smoking leads to CHD has not been clear. To learn more about how genetics affect the interplay between smoking and heart disease, the researchers pooled genetic data on more than 140,000 people from 29 previous studies. They analyzed 45 small regions of the genome that have been previously associated with a heightened risk of CHD. They hypothesized that for some of these regions, the associated heart risk would be different in smokers than in non-smokers.

The analysis showed that a change in a single DNA "letter" on chromosome 15, near the gene that expresses an enzyme (ADAMTS7) produced in blood vessels, was associated with a 12 percent reduction in heart risk in non-smokers. However, smokers with this same variation had only a 5 percent lower risk of CHDreducing by over half the protective effect of this genetic variation.

DNA variations located near a gene sometimes inhibit the gene's activity, causing below-normal levels of the protein it produces. In this case, the researchers discovered that the single-letter DNA variation that protected patients from CHD resulted in a significant decline in the production of ADAMTS7.

In a separate recent mouse study, Dr. Reilly's lab demonstrated that genetic deletion of ADAMTS7 reduced the buildup of fatty plaques in arteries, suggesting that blocking the production or function of this enzyme might be a way to lower the risk of CHD.

In the current study, when the researchers applied a liquid extract of cigarette smoke to coronary artery cells, the cells' production of ADAMTS7 more than doubled, supporting the conclusion that smoking may counteract the genetic protection from CHD by increasing the level of ADAMTS7 in the artery wall.

"This has been one of the first big steps towards solving the complex puzzle of gene-environment interactions that lead to CHD," said lead author Danish Saleheen, PhD, assistant professor of biostatistics and epidemiology at the Perelman School of Medicine at the University of Pennsylvania.

In future studies, the researchers hope to establish exactly how the ADAMTS7 variants protect against CHD, how cigarette smoking affects the activity of the gene that produces the enzyme, and whether reducing or inhibiting ADAMTS7 can slow the progression of atherosclerosis due to cigarette smoking.

"This study is an important example of the emerging field of precision medicine and precision public health," said Dr. Reilly. "Through these large-scale genetic studies, we're beginning to understand the genetic variations that drive risk in response to certain environmental exposures or lifestyle behaviors. Not everyone reacts the same to the same exposures or behaviors. For example, some people who don't exercise develop diabetes while others do not. So, instead of saying there are rules for everybody, we can specify which interventions will be especially beneficial for specific populations or individuals and focus our health resources more efficiently."

The study is titled, "Loss of Cardio-Protective Effects at the ADAMTS7 Locus Due to Gene-Smoking Interactions."

Explore further: Scientists identify new therapeutic target for coronary heart disease

More information: Danish Saleheen et al. Loss of Cardio-Protective Effects at theLocus Due to Gene-Smoking Interactions, Circulation (2017). DOI: 10.1161/CIRCULATIONAHA.116.022069 , circ.ahajournals.org/content/early/2017/04/20/CIRCULATIONAHA.116.022069

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Smoking-related heart disease tied to effects of a single gene - Medical Xpress

The recent FDA approval of 23andMes direct-to-consumer genetic testing is an interesting and inevitable milestone in the dissemination of medical knowledge to the public. However, we must proceed with caution to ensure that this information is understandable and not anxiety provoking.

Over the past two decades, we have seen a dramatic increase in our knowledge about the genetic basis of many diseases. Most of the clinical use of this genetic information has been to counsel selected populations that were deemed high risk based on family history or other features. The information was conveyed to patients under the guidance of medical professionals who are skilled at interpreting the prognostic implications of the test results and who can advise patients about treatment options.

Recent advances in technology permit the whole genome to be screened for serious diseases at reasonable costs. Given the thirst by consumers for access to health information, direct-to-consumer testing was bound to happen.

Overall, I believe that readily accessible genetic information has the potential to improve public health if also accompanied by access to medical interpretation and counseling regarding test results.

For many, the implications of genetic mutations are quite complex, as they may only indicate increased risks of disease, not the inevitability of disease occurrence. Additionally, implications for social and family consequences of test results must be addressed. It is interesting that the first set of diseases chosen by 23andMe are diseases with public fear factors such as Alzheimers and Parkinsons rather than the more lethal conditions that can be identified by genetic testing. For example, the American College of Medical Genetics (ACMG) has published a list of 56 serious diseases that may be incidentally found during genetic screening (during research studies or exams for other conditions). These include genetic predispositions to cancer, heart disease, and neuromuscular diseases. Careful medical counseling is required when these genetic alterations are identified.

It is not a question of if but rather when the public will demand over-the-counter access to screening for more serious diseases, including the BRCA breast cancer genes or hereditary colon cancer genes.How the public will handle this information is unclear, but most studies on medically supervised genetic testing have been favorable. And based on the feedback I hear from patients and their families in my oncology practice, they would all encourage greater public awareness and testing for these conditions.

But even before we reach that stage, the current lack of required professional counseling regarding the interpretation of test results is troubling. The cautionary concerns that have bubbled up in recent years around Dr. Google and the surge in self-diagnosis from sites such as WebMD will need to extend to genetic testing. For example, some individuals may welcome the reassurance that they do not carry high-risk genes. But a positive test result could be met with great angst without understanding that for some mutations the risk of disease can be high, but for other genes the risk can be low. This is where counseling is critical.It will be incumbent on test manufacturers to provide access to genetic counselors so the results can be placed into proper context.The public must be properly informed that merely carrying a certain gene does not doom an individual to developing a disease, but similarly must be counseled when medical actions are appropriate.

Although direct-to-consumer advancement and FDA approval should be celebrated, it is by no means an endorsement to open a floodgate of genetic testing. When we consider the growing consumerization of medicine and the reduction in genetic testing costs, this was a logical progression. I hope that we will see more in terms of increasing access to medical advances and that more private enterprises will step up to satisfy the publics thirst for credible medical information. Other advances in technology including healthcare monitors and wearables, home diabetes monitoring and medication reminders will place consumers in more control of their own health. Changes in data exchange, including greater access to electronic medical records and direct transfer of laboratory results, will also help patients stay aware of their diseases.

The increased benchmarking of doctors and hospital systems will also help consumers make more informed choices about where to receive healthcare. What the medical community learns from these advancements and how consumers respond will we all be willing to give more for science or vice versa? could easily accelerate our path to moonshot. Or perhaps we will see a recoil and consider this a time of oversharing of too much information. Time will tell. But in the meantime, I look forward to the next logical step: More channels and greater access to counseling so patients are not interpreting these results in a vacuum.

Photo: DrAfter123, Getty Images

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This is the direction direct-to-consumer genetic testing needs to take - MedCity News

People who smoke cigarettes may boost their risk of clogged heart arteries by weakening a gene that is otherwise protective of these important blood vessels, US researchers said Monday.

The findings point to a genetic explanation for how smoking can lead to the plaque buildup that stiffens arteries and causes heart disease, said the report in the journal Circulation.

"This has been one of the first big steps towards solving the complex puzzle of gene-environment interactions that lead to coronary heart disease," said co-author Danish Saleheen, assistant professor of biostatistics and epidemiology at the Perelman School of Medicine at the University of Pennsylvania.

Researchers pooled genetic data on more than 140,000 people from more than two dozen earlier studies, with a particular focus on regions of the genome that have been previously associated with a higher risk of plaque buildup in the heart's arteries.

"A change in a single DNA 'letter' on chromosome 15, near the gene that expresses an enzyme (ADAMTS7) produced in blood vessels, was associated with a 12 percent reduction in heart risk in nonsmokers," said the report.

"However, smokers with this same variation had only a five percent lower risk of coronary heart disease -- reducing by over half the protective effect of this genetic variation."

Follow-up lab studies showed that in cells that line arteries of the human heart, the production of the enzyme ADAMTS7 dropped significantly when the cells contained this single-letter DNA variant.

Another experiment showed when coronary artery-lining cells were exposed to the liquid extract of cigarette smoke, the cells' production of ADAMTS7 more than doubled.

If researchers can find other ways to inhibit this enzyme, they might be able to help smokers and others at heightened risk of coronary heart disease, said co-author Muredach Reilly, director of the Irving Institute for Clinical and Translational Research at Columbia University Medical Center.

Cigarette smoking is known to cause about one in five cases of coronary heart disease, and is linked to approximately 1.6 million deaths worldwide each year.

"Through these large-scale genetic studies, we're beginning to understand the genetic variations that drive risk in response to certain environmental exposures or lifestyle behaviors," said Reilly.

"Not everyone reacts the same to the same exposures or behaviors. For example, some people who don't exercise develop diabetes while others do not," he added.

"So, instead of saying there are rules for everybody, we can specify which interventions will be especially beneficial for specific populations or individuals and focus our health resources more efficiently."

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Smoking Weakens a Gene That Protects Arteries - Newsmax