4:07 PM
May 18, 2017
 |  BC Innovations  |  Product R&D

Making cells compute

The momentum is building in synthetic biology; CAR Ts stand to benefit

With efficiency in DNA engineering continuing to grow, and an increasing convergence between engineering and biology, synthetic biology -- in its “truest” form -- is coming within striking distance of translating preclinical proof of concept breakthroughs to the clinic.

And while chimeric antigen receptor (CAR) T cells could be prime beneficiaries of the advances, some basic tenets of the technology might present IP lawyers with new challenges.

The field is still carving its own definition and its boundaries, as companies across the spectrum adopt the “synthetic biology” label, blurring the line between simple engineering of individual genes and the original concept -- which involves the artificial design and construction of new biological systems.

In its strictest definition, synthetic biology involves incorporation of two or more artificial components in a cell to carry out a novel combined function. That means that simply introducing a protein on an expression vector doesn’t qualify, but introducing two genes to a cell to express a protein under a set of qualified, contained circumstances does.

Broader use of the label encompasses the generation of the components to enable that process, such as synthetic biological building blocks ranging from artificial DNA bases to chimeric genes.

Although the field emerged in the early 2000s, it has been primarily tapped to engineer biosynthetic pathways in bacteria for creating industrial products such as biofuels or ingredients for cosmetics. The highest profile achievement thus far in drug development has been the engineering of yeast to generate artemisinic acid, the precursor to the anti-malarial drug artemisinin, which came out of a 2008 partnership between Amyris Biotechnologies Inc. (now Amyris Inc.), sanofi-aventis Group (now Sanofi) and Institute for OneWorld Health. Sanofi began marketing yeast-derived artemisinin in 2014.

But according to Wendell Lim, the field is now returning to applications in which “the cell itself is not just a factory, it’s also a computer.”

“This field started with the computing capabilities of genetic regulatory networks, but those took a back seat as metabolic engineering became a lead application for synthetic biology. But now, I think we’re really coming back to harnessing the unique capabilities of cells to be complex sensing and computing devices,” he said.

Lim is a professor of cellular and molecular pharmacology at the University of California San Francisco and scientific founder of Cell Design Labs Inc.

“What attracted me about living biology that computes signals is that no other modality can sense and respond in this way.”

Jose-Carlos Gutiérrez-Ramos, Synlogic

Cell Design Labs is one of a spate of newcos formed in the last few years that are engineering artificial sense and response circuits in cells. The company, which focuses on cellular immunotherapies, raised $34.4 million in a venture round last June led by Kleiner Perkins Caufield & Byers. Kite Pharma Inc. also invested, and signed a deal with Cell Design to use the startup's CAR T cell on-switch technology, dubbed Throttle Switch, to make therapies for acute myelogenous leukemia (AML).

One of the leaders in the new crop is Synlogic Inc., which was founded in 2014 with backing from Atlas Venture. Following a $29.4 million Series A in 2014 and a $40 million Series B in 2016, the company disclosed on Tuesday a $42 million Series C round and announced it will become a publicly traded entity via a reverse merger with Mirna Therapeutics Inc.

CEO Jose-Carlos Gutiérrez-Ramos told BioCentury he was drawn to the idea of synthetic circuit-based therapeutics by the multi-functionality and control they afford.

“What attracted me about living biology that computes signals is that no other modality can sense and respond in this way,” said Gutiérrez-Ramos. “You can have potency with conventional drugs, but they can’t sense. With other living therapeutics, I think the potency piece and the control of sensing and responding is more blunted.”

Atlas Venture partner and Synlogic chairman Peter Barrett said that logic prompted his firm to invest.

“What we started to realize is that there are things those cells can do that are very difficult for small molecules and antibodies to do, and that’s to provide a full...

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