Eyeing in-vivo editing, Mammoth licenses Jennifer Doudna’s new CRISPR enzyme
Last month, Jennifer Doudna revealed in Science a new, “hyper-compact” CRISPR enzyme that was half the size of traditional CRISPR enzymes and could, she suspected, offer a new, more versatile tool for gene editing.
Now, the University of California-Berkeley has licensed that enzyme, known as Casφ, exclusively to a biotech startup she and two former students set up three years ago: Mammoth Biosciences. It’s the second new CRISPR protein Mammoth has licensed from Doudna’s lab, after they licensed Cas14 in 2019.
“Cas9 is like a standard sized system, Casφ is like a micro-sized sized system, you could say,” CEO and co-founder Trevor Martin told Endpoints News. “It has huge advantages in terms of delivery. There’s initial kind of evidence in the paper that’s super-exciting around flexibility and targeting.”
Mammoth has been primarily known as a diagnostic company, most notably developing a CRISPR diagnostic for Covid-19 that has been authorized by the FDA and which Mammoth and GSK are trying to turn into a rapid, point-of-care test. But the company, Martin notes, has spent much of the last three years on basic biology, developing new CRISPR systems that can offer advantages not only for testing but also for therapeutics and gene editing.
In that effort, they’re joined by academic labs at Berkeley and MIT and biotechs such as Arbor, which developed a new enzyme called Cas13d and has a “search engine” platform to find other proteins. Doudna and former student and Innovative Genomics Institute entrepreneurial fellow Benjamin Oakes are also launching Scribe Therapeutics around a new enzyme they call CasX.
Casφ’s small stature, Martin said, could make it a good fit for delivering in-vivo. One of the more difficult applications for CRISPR, scientists only just did for the first time in a patient this year. Casφ’s size should make that easier, by letting you fit a system into the AAV vectors commonly used for gene therapy. It could also be used for what Martin calls “CRISPR-plus” — technologies like base-editing or other applications that might require combining multiple CRISPR systems into a single fusion.
For those, he said, you want components “as small as possible, so you have room to fit all this other machinery.”
Martin noted in particular that Casφ doesn’t require some of the extra RNA other CRISPR systems do to hit their targets; it can function as its own homing mechanism.
“Many of these properties are going to be truly critical for realizing the potential of CRISPR,” he said.
Correction: An earlier version incorrectly attributed the invention of CasX. It came out of Doudna’s lab.