The SynBio Mashup is a weekly review of articles and news related to synthetic biology and metabolic engineering. While we share most of this on our twitter feed, if you need to catch up on this week’s news just read ahead!
A team of synthetic biology researchers led by Christina Smolke at Stanford University engineered yeast to produce thebaine, an opiate precursor to morphine and other painkiller medications, from primary metabolism. The team also demonstrated that with further strain development the genetically modified yeast could make hydrocodone, a widely used painkiller currently made from thebaine recovered from poppy plants
Previously, synthetic biologists have generated products using only a small number of added genes from a small number of species. This team added 21 genes to make thebaine and 23 genes to make hydrocodone from a number of distinct species including three different poppy species, rat, Goldthread, and Pseudomonas bacterium. Although this seems like a significant advancement in drug development, the microbes will need to increase thebaine production 100,000 fold before pharmaceutical companies become interested in using the genetically modified yeast as producers of opiates for medications.
The team stopped short of adding all of the genes necessary to generate morphine because biopolicy makers fear that if a strain of yeast that makes morphine gets into the hands of illicit drug makers, they could use it to easily generate heroine. Policy makers may need to ensure that no strains are developed for the production of illicit drugs or that genes are added to prevent opiate generating genes from surviving outside of controlled laboratory settings. Read the full paper here!
Intrexon’s recent stock price decline did not stop it from acquiring Oxitec, a British company that engineers genetically modified insects, for $160 million in total considerations. Oxitec engineers males of a number of target species whose progeny do not reach adulthood when they mate with wild-type females. Continual release of these GMOs can decrease population sizes of specific target insects that consume crops and cause diseases below harmful threshold without using traditional insecticides and their ecological consequences.
In their current pipeline, Oxitec has genetically modified diamondback moths, pink bollworms, medflies, mexflies and olive flies to prevent crop destruction and also mosquitos to prevent Dengue fever, Chikungunya, and Yellow fever. At this point, only the Aedes aegypti OX513A mosquito construct to control Dengue fever is at the commercial optimization phase of development. It has obtained regulatory approvals for import and contained testing in Brazil, Cayman Islands, France, India, Malaysia, Singapore, Thailand, USA and Vietnam. Open field trials have taken place in Grand Cayman and Malaysia, and are currently also underway in Brazil.
Revivicor, a company focused on eventually xenotransplanting genetically modified porcine tissue into humans, reported that a xenotransplantation of a pig heart into a baboon was not rejected for 945 days and a kidney was not rejected for a record-breaking 136 days. The heart transplant was “heterotropic”. It was not critical to the survival of the baboon because although the heart was connected to the baboon’s circulatory system and able to beat, the baboon’s own heart remained in place to sustain life. The heart only failed afterEd the baboon was taken off immunosuppressant medication. The xenotransplantation of the kidney, however, was considered the longest life-sustaining xenotransplantation between a pig and a primate.
The scientists at Revivicor knocked out the pig’s alpha 1,3 galactosyltransferase gene, preventing the placement of galactose on branched sugar chains on cell surfaces that primate immune systems recognize and reject as part of the Hyperacute Rejection response. They also inserted five human genes into the transplanted organs. They inserted CD46, a cell surface protein that helps prevent the immune system from attacking host tissue, and a human version of thrombomodulin, a molecule that prevents clotting in blood vessels.
While these results seem very promising for xenotransplantation, pig to human transplants are still more than a few years away. Organs that are not rejected have not yet been developed because as one rejection problem is solved, another one presents itself. Revivicor is continuing their preclinical trials in primates and eventually intends to start clinical trials in humans if the results are promising. The first human xenotransplants will be used to sustain life while awaiting a human donor.
Editas, a genome editing company with specific expertise in CRISPR/Cas 9 and TALENs technologies received $120 Million in Series B funding on August 10th, 2015. Boris Nikolic, M.D., Bill Gates’ former chief advisor for science and technology, founded bng0; a U.S. based Investment Company with the financial backing of Bill Gates with the specific purpose of funding Editas. As part of the funding agreement, Nikolic is joining the Board of Directors at Editas. In addition to bng0, a team of thirteen “cross-over” investors took part in the Series B funding.
The funding should keep the company afloat for the next three years, allowing it to advance multiple new therapies into clinical trials. Editas is concerned with gene therapy and the delivery of CRISPR/Cas9 proteins into the cells of sick patients using vectors. Editas’ first product likely to be tested in humans is their treatment of Leber’s congenital amaurosis type 10, a genetic disease that causes blindness. This is a good candidate for Editas’ delivery system because it is easy to deliver a vector to the eye and the condition is caused by a single substitution mutation that can be deleted. Editas is also working on curing sickle-cell anemia.
Editas also signed a deal with Juno Therapeutics in May 2015 to develop chimeric antigen receptor (CAR T) and high affinity T-cell receptor (TCR) therapies to treat blood borne cancers and solid tumors. Editas and Juno will edit a patient’s own T-cells to better recognize and destroy cancer cells. As part of that agreement, Juno paid Editas $25 million upfront and will pay them an extra $22 million in research support over the next five years. Editas will also be eligible for royalties and milestone payments upwards of $230 million for each of three separate programs.