In the bid to lock up patent rights to a growing suite of gene editing technologies, Arbor Biotechnologies has acquired a small startup founded by MIT scientist and CRISPR pioneer Feng Zhang, the company exclusively told Endpoints News.
Zhang’s startup, Serendipity Bioscience, has never disclosed how much funding it raised, and Arbor — which Zhang also co-founded — wouldn’t say how much it paid. But Arbor now holds the keys to four new families of gene editing enzymes discovered in Zhang’s lab in recent years, each the subject of major scientific publications.
One of those enzyme families, known as Fanzors, are cousins of CRISPR found in certain plants and animals — a surprise discovery after decades of work had only turned up gene editing enzymes in microbes. Another family of so-called IsrB enzymes naturally nick a single strand of the DNA helix instead of cutting both strands, a useful feature for some forms of editing.
Both are tiny compared to Cas9, the most widely used and studied CRISPR protein. That could make them easier to squeeze into delivery devices that can reach more parts of the body than current methods.
Zhang has founded numerous gene editing companies, many of which raised hundreds of millions of dollars from private investors. As his lab debuted new CRISPR tools, so came new, well-funded startups. Many experts expected that would be true with his several recent crops of new enzymes. Yet with minor exceptions, the new enzymes turned out to be similar to old ones.
Feng Zhang“Initially we were hoping that there would be more distinguishing features,” Zhang told Endpoints. “But it turns out that these enzymes really are just a more compact version of the enzymes that people are developing for therapeutic applications.”
With dozens of competitors in gene editing and funding comparatively tough to come by for early-stage biotechs, Zhang settled for selling Serendipity to Arbor, which he helped start in 2016. It wasn’t immediately clear what ownership stakes, if any, Zhang has in the two companies.
“Given the biotech funding climate, and just the overall macroeconomic situation, it makes a lot more sense to partner with a strong group that has all the infrastructure, and all the capabilities already established, so that these things can get into the clinic or some type of product development sooner,” Zhang said.
‘Not just stamp collecting’
Several biotech startups, including Arbor, were founded on the belief that Cas9 was not the end of the road for CRISPR. Mammoth Biosciences and Scribe Therapeutics were based around particular Cas enzymes discovered in Jennifer Doudna’s lab at UC Berkeley, while Arbor and Metagenomi, which went public earlier this year, launched with expansive remits to search the earth for new and interesting CRISPR enzymes.
“Everyone had Cas9, but it was clear that it wouldn’t be the tool for all things,” Arbor CEO Devyn Smith told Endpoints. “We are not just stamp collecting.”
All of these companies have faced a tough balance between discovering and refining new enzymes and actually making a therapy with them. None of them has entered the clinic, although Arbor believes that next year it could become the first to infuse a CRISPR therapy that’s not based on Cas9 into humans.
Smith said there’s “relatively little incremental value” in finding further enzymes for knocking down or excising problematic genes — the focus of its first programs for rare liver diseases and the neurologic condition ALS.
But he thinks new enzymes are important for newer editing methods such as prime editing and gene integration methods, which combine a gene editing enzyme with other proteins to make bigger or more complex changes to DNA, including replacing or inserting genes.
In addition to Fanzor and IsrB enzymes, Zhang said that Arbor will get access to compact TnpB enzymes, which can hook up with other proteins called transposases to insert large stretches of DNA in particular parts of the genome. A fourth group of enzymes, the Cas5-HNH family, could help improve the specificity of editing and may be useful in cell therapies, he added.
Smith said that discovering new enzymes, building a company from scratch, and getting therapies into the clinic is such a lengthy process that he doubts investors will be rushing to lavishly fund new startups centered around new gene editing enzymes.
“Unless you have something differentiating, from a target perspective, I am not sure there is an appetite for it,” he said.
Editor’s note: This story was updated to state that Arbor’s first program could enter the clinic next year, not this year. The company plans to file an IND later this year.