Just How Smart Is Smart Medicine? MIT Scientists Are About To Find Out

We have smart phones, smart cars and now, with the advent of a new class of “living medicines,” we’re on the verge of having smart therapeutics.

Synlogic, a Cambridge, Massachusetts-based MIT spin-out, is applying engineering principles to biology to treat diseases in a unique way with Synthetic Biotic™ medicines.

Developed by pioneers of synthetic biology, MIT’s Jim Collins and Tim Lu, the clinical stage company is engineering these “smart medicines” by programming beneficial probiotic bacteria to perform functions that people with certain genetic or acquired metabolic diseases cannot. They are designed to sense and respond to their environment while performing a specific therapeutic task.



Synlogic Lab


Once a synthetic biotic medicine is ingested—for now in pill form—the engineered therapeutic bacteria go to work performing whatever task they have been programmed to do. Much like our smart technology today can be programmed to perform tasks of daily living, these smart, living medicines can be programmed to specifically perform a therapeutic function depending upon the target disease.

For example, the company’s lead product candidate, SYNB1020, is in development to treat hyperammonemia due to liver cirrhosis and urea cycle disorders. Patients with this disorder are missing an enzyme for maintaining healthy levels of ammonia. Because of this, they can experience elevated, often toxic levels of ammonia that can lead to brain injury and even death.


Like a robot vacuum for the gut, SYNB1020 has been specifically engineered to convert the excess ammonia to a harmless metabolite.

The MIT scientists started with probiotics because they are safe and beneficial to the intestinal tract but also because people are familiar with them. “We are basically creating synthetic probiotics that can be taken in the form of pills and can be used therapeutically,” said Collins, co-founder of Synlogic, Henri Termeer Professor of Medical Engineering & Science and Professor of Biological Engineering at MIT. He is also a core founding faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University, an institute member of the Broad Institute of MIT and Harvard as well as a charter fellow of the National Academy of Inventors. Collins’ patented technologies have been licensed by over 25 biotech, pharma and medical devices companies, and he has helped to launched a number of companies, including Sample6 Technologies, Synlogic and EnBiotix.

Collins said probiotics are also good organisms to manipulate as the engineering of these bacteria are already well understood by scientists. “We engineer a bacterium so we can put a genetic circuit in it to produce something that’s missing allowing it to carry out a specific activity that will be beneficial for patients with specific disease,” Miller said.



James J. Collins, co-founder of Synlogic.

In the example of hyperammonemia, a buildup of ammonia is toxic to the brain, Collins said. It can cause cognitive impairment and can lead to coma and even death. “A living therapy will be taken by mouth as a pill, like a probiotic. As it moves through the intestinal tract doing its job of grabbling ammonia that shouldn’t be there, it’s effectively vacuuming up the ammonia before it can get into the rest of the body, thus taking the pressure off of the liver. The idea is that the patient would take the medicine every day and compensate for the fact that the liver is not working well. It would keep patients out of the hospital and improve their daily life.”

Currently, Synlogic’s drug candidates are focused on treating rare, genetic metabolic diseases, but they say other major diseases are absolutely on their radar screen. And SYNB1020 could potentially offer hope to patients with a myriad of reasons for poor liver functioning, including bile disease, fatty liver and even alcohol abuse.

Synlogic is currently developing medicines that address disease from a base of operation in the gut microbiome, and its pipeline includes synthetic biotic medicines for the treatment of inborn errors of metabolism (IEM).



Synlogic lab.

But the company says it will eventually apply its proprietary platform, Synthetic Biotic™ medicines, to create other biotic medicines for the treatment of major diseases involving inflammation, metabolism, oncology and the central nervous system (CNS) including the company’s second program, SYNB1618 (for phenylketonuria/PKU) which is expected to enter the clinic this year.

“We feel there is potential to use this kind of approach for patients with a whole variety of disorders,” said Paul Miller, chief scientific officer of Synlogic. A microbial geneticist by training, Miller is accountable for all aspects of discovery research and platform expansion at the company. Before joining Synlogic in 2014, Miller was the vice president of infection biology at AstraZeneca. Before that, he was the chief scientific officer for antibacterial research at Pfizer.

“Each engineered probiotic would be specific to each disorder. We start with rare diseases because we know what the bad actor is, like in the example of high ammonia levels. We’re not saying we can treat every problem humans have, but we think there are a large number of diseases that could be addressable with a biologically engineered approach.”



Paul Miller, chief scientific officer of Synlogic.

The synthetic medicine SYNB1020 is currently in clinical trials with patients with high levels of ammonia. Synlogic will be treating patients over the course of the year and hopes to have data to share by the end of 2018. The company already established dosage levels with an earlier study. Miller said in that study they found the medicine to work well and be well-tolerated while in the body and easily cleared from the body after its use is discontinued.

“If we are successful with these current trials, this will be the first time a living medicine of this type has shown a benefit for patients with these types of metabolic diseases,” Miller said. “Nobody’s ever used one of these engineered probiotics and shown a benefit in real patients.”


Synlogic, Inc., (Nasdaq: SYBX) announced last month that preclinical data from its immuno-oncology (IO) program will be presented at the upcoming annual meeting of the American Association for Cancer Research (AACR) being held April 14 to 16, 2018, in Chicago.

The presentations will cover how bacteria genetically engineered to consume metabolites that help tumors evade and impair the immune system may enhance anti-tumor activity. The company is slated to file its first Investigational New Drug (IND) Application with the FDA in oncology in 2019.


In addition to developing its own smart medicines, Synlogic has partnered with AbbVie and Ginkgo Bioworks to enhance discovery efforts and further accelerate the development of its novel gut-based therapeutics.

Collins' partner and co-founder of Synlogic, Tim Lu, leads the Synthetic Biology Group in the Department of Electrical Engineering and Computer Science and the Department of Biological Engineering at MIT. He is a core member of the MIT Synthetic Biology Center where his research focuses on engineering integrated memory and computational circuits in living cells using analog and digital principles, applying synthetic biology to tackle important medical and industrial problems and building living biomaterials that integrate biotic and abiotic functionalities.



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