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His goal: Make the bugs in our bodies work for us

Our bodies are full of bugs. They’re everywhere, hanging out on our skin, reproducing in our gut, growing on the glistening surface of our eyes. These bacteria, it turns out, don’t just beget other bacteria. They also beget scientific paper after scientific paper, which, in turn, beget headline after headline.

But for all our talk of microbiomes, we aren’t all that great at shaping them, says Dr. Timothy Lu, an associate professor of biological engineering and electrical engineering at the Massachusetts Institute of Technology.

He’s trying to change that. The two companies that have been spun off from his labwork are looking to manipulate the bacteria in our bodies in very different ways, to solve very different problems.

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Eligo Bioscience, which in September secured $20 million in Series A funding, is working on “nanobots” to more precisely treat bacterial diseases. Synlogic, which went public in May, on the other hand, announced that the top-line results of an early trial were positive: Its “living medicines” to treat genetic urea cycle disorders seemed safe when tested in healthy volunteers.

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STAT caught up with Lu to find out how the science in his lab helped give rise to the companies he co-founded.

Can you tell me about the current methods for shaping the microbiome?

Our existing strategies for being able to modulate the microbes inside of us — the microbiome — are relatively crude. The predominant way we modify our microbiome is through the use of antibiotics. It’s sort of like carpet-bombing all the bacteria that’s living inside of us. It’s not very precise.

How have you tried to address that?

We’ve developed two technology bases. The first is what led to Synlogic: Can we actually genetically modify the microbes that live inside of us so that when they are inside of your gut, those microbes can sense what’s going on and then make drugs or different therapeutic factors that actually modulate disease? So that’s sort of an additive approach in that we’re actually gene-modifying probiotics or commensal bacteria and then we’re going to put them into the body.

Eligo is doing the opposite. There are a lot of bacteria already inside of the body. Can we actually remove specific members of that microbiome in a targeted way, rather than giving antibiotics? So we’ve been developing tools that use bacteriophages —which are basically bacterial viruses — to infect and target those bacteria. On top of that, Eligo [will] then incorporate a CRISPR-Cas system into bacteriophages so that once they are delivered into the bacteria, they can very precisely discriminate between whether this a “good” bacteria versus a “bad” bacteria, and only kill the bad guys.

What about the science behind Synlogic’s first potential treatments?

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With the first couple of therapeutic programs, we’ve decided to focus in on diseases of inborn errors of metabolism. These are typically kids that are born and they lack certain enzymes that most people have to help them break down specific toxins in their bloodstream. As a result those toxins build up and cause all sorts of developmental and neurological issues. What we’ve done is to gene-modify the bacteria to be able to consume and degrade those toxins.

We have also engineered bacteria to be able to make specific drugs in the gut. So it’s not only chewing up bad things, but it would also be able to deliver good things into the system, and we think those should have applications even more broadly in areas like cancer or inflammatory bowel disease or other areas.

What are some of the challenges?

There are a lot of association studies that are being done now that link the presence of certain bacteria or their metabolites to specific diseases, but not as much data has been available on the causative proof that this bacteria or this metabolite is the sole thing that’s involved in a disease.

That’s one of the questions: Can you actually engineer a bacterium that’s potent enough and that addresses the right sort of causative molecule that is responsible for these human diseases? That’s in part why Synlogic has chosen initially to focus on really well-defined metabolic disorders. It’s pretty well-understood that in urea cycle disorder, or in PKU, what the offending molecule is. In urea cycle disorder, it’s ammonia, and in PKU, it’s phenylalanine.

If you went after a more complex disease like cancer or autism, at this point, the science is not out there in terms of what molecules you’d need to make or create. That’s a lot more challenging.

Eric Boodman can be reached at eric.boodman@statnews.com. Follow him on Twitter @ericboodman. Follow Stat on Twitter: @statnews.