This article is sponsored by Ginkgo Bioworks.
In the past ten years, the human microbiome has garnered an incredible amount of traction as a research subject and space for health intervention. During the rise of the microbiome, cultured foods like yogurt, kombucha, and kefir have enjoyed an industry boost owing to their capacity to make the gut a better, healthier place. But soon, it seems, cultured foods will be joined and overshadowed by a more sophisticated counterpart: the designed probiotic.
Designed probiotics go beyond our current ability to modulate the microbiome by bolstering its good actors and cutting out its bad ones. We’re talking about microbes that have been purposefully and rationally designed to contribute to the health of their host. As knowledge of the gut microbiome’s nuances and its relationship to disease states grows, these fit-for-purpose therapeutic microbes are entering the realm of the possible. Multiple groups are endeavoring to put together combinations of microbes and even genetically retrofit microbes with novel metabolic capabilities in order to achieve a particular health outcome. Namely, some synthetic biologists are undertaking to design microbes that function not as a general supplement, but as a drug for treating a specific indication.
There are a few different ways in which genetically modified live biotherapeutic products, as the FDA calls them, can be made to function as living medicine. One way is that, with a little bit of tweaking, probiotics can be designed to replace or supplement a particular metabolic step or process that is missing or damaged in an individual. Cambridge-based Synlogic is leading the way for engineered probiotics – or Synthetic Biotic medicines as they call them. This past year, Synlogic has been working on developing a strain of modified E. coli for use in patients whose systems cannot process nitrogen rapidly enough, causing a buildup of excess ammonia that can lead to neurologic and behavioral symptoms. Synlogic’s microbial drug is capable of taking up ammonia and transforming it into arginine, an essential and harmless building block of proteins. This Synthetic Biotic medicine is already in Phase 1 trials and is a huge advancement for this specific program and the future of living medicines.
Beyond the current pipeline, the complex connections between the microbiome and conditions ranging from obesity to immune disorders to neurological conditions indicate that engineered probiotics may be able to target a wide array of diseases. To explore the breadth of what is possible, Synlogic has also partnered with Ginkgo Bioworks to design novel living medicines to treat neurological and liver disorders. Together, the two companies plan to design and test many prototype probiotics at high throughput and grow their portfolio of living medicines with additional pharmaceutical partners.
Designed probiotics are also being explored as a way to enhance the effectiveness of other non-probiotic therapies. For example, there is an increasing amount of research that shows the composition of the gut microbiome can have consequences on the effectiveness of certain immunotherapies for cancer treatment and reducing side effects. In another scenario, genetically modified bacteria are being used for the selective delivery of anti-cancer drugs to treat inoperable tumors.
Synthetic biology is paving the way for designed probiotics to take on an entirely novel application in the form of living medicine. There is enormous potential to improve the health of the human body and resolve various ailments by manipulating the millions of microbes that call it home.
Both Jason Kelly and Christina Agapakis will be speaking at SynBioBeta 2018.