Scribe Therapeutics launches to explore next-generation CRISPR technology

Scribe Therapeutics, a biotech firm focused on developing next-generation gene-editing technology, has raised $20 million in its first major round of financing, backed by Andreessen Horowitz. The firm separately unveiled a deal with Biogen to develop CRISPR-based treatments for amyotrophic lateral sclerosis (ALS).

Scribe was cofounded in 2018 by several University of California, Berkeley, scientists, including gene-editing pioneer Jennifer Doudna and protein engineer Benjamin Oakes, who at the time was an entrepreneurial fellow at the Innovative Genomics Institute, where Doudna is president. Their goal was to engineer a newly discovered class of Cas proteins to make them behave better as therapies than the original CRISPR-Cas9 gene-editing system.

The original system was found in bacteria, which use it to recognize and chop up DNA from invading pathogens. Scientists, including Doudna, quickly realized the system could be co-opted to make precise cuts to human DNA. The tool set off a race among companies trying to use it to address the genetic mutations underlying many diseases.

But even with its promise, the CRISPR-Cas9 system comes with “evolutionary baggage,” Oakes, who is now CEO of Scribe, says. Those systems “aren’t designed to work within the context of the human cell or even the human genome,” he says, complicating efforts to turn the technology into drugs.

Several years ago, a group of Berkeley researchers set out to look for other Cas proteins. By sifting through the genomes of microbes that live in a variety of settings—groundwater, acid-mine drainage biofilms, and the digestive tract of infants—they identified two new classes of proteins, CasX and CasY.

Oakes, working in Doudna’s lab, helped to characterize the features of CasX, reporting in 2019 several ways the class improves upon Cas9. CasX is smaller, allowing it to be more easily packaged inside of adeno-associated viruses for therapeutic delivery, and can more efficiently and precisely snip DNA.

Scribe scientists have spent the past two years engineering CasX to arrive at a collection of proteins, which it calls X-Editing molecules, that perform as well or better than all of the other CRISPR-based gene-editing systems, Oakes says.

Now, the Scribe team, which has grown to almost 25 people, is focused on turning those molecules into therapeutics. Scribe made public its first big pharma partnership, scoring $15 million from Biogen to develop CRISPR-based drugs to treat ALS.