Mammoth exclusively licensed IP covering one of the newest families of CRISPR enzymes, Cas14, from the University of California Berkeley. The new license adds a third group of CRISPR enzymes to the diagnostics company’s toolbox.
While the IP landscape covering CRISPR-Cas9 for therapeutic applications is becoming increasingly complex following the conclusion of the interference case between a Regents of the University of California group and the Broad Institute of MIT and Harvard, the IP covering CRISPR-associated protein 14 (Cas14) and other CRISPR enzymes is not involved in that dispute.
CRISPR pioneer Jennifer Doudna first described Cas14 as a CRISPR-associated enzyme from archaea, rather than bacteria, in a Science study published last year (see “UC Berkeley Group Identifies New Cas Enzyme”).
Doudna is a professor of chemistry and of biochemistry and molecular biology at the University of California Berkeley and a co-founder of several CRISPR companies including Mammoth Biosciences (San Francisco, Calif.).
Enzymes filling the growing CRISPR toolbox have varied properties that fit different applications (see “Modality Moves at Vertex”).
Mammoth co-founder and CEO Trevor Martin told BioCentury that Cas14 makes a good tool for diagnostic applications because it has a collateral cleavage property, targets single-stranded DNA and doesn’t require a protospacer adjacent molecule (PAM) sequence — a short nucleotide sequence adjacent to a target site that’s required by many CRISPR enzymes to bind.
Collateral cleavage occurs when a CRISPR enzyme indiscriminately cleaves DNA or RNA after cutting its target site. That is an ideal property for diagnostics, which can be designed to cleave a fluorescent reporter to emit a signal only when a target is present.
Martin noted that Cas14 will be particularly useful for detecting DNA virus targets, and the lack of a PAM sequence means it can be designed to target any site.
Mammoth hasn’t disclosed any specific indications for its diagnostics platform, but Martin said the company is interested in infectious diseases.
Mammoth has exclusive rights to Cas14 for all applications, including therapeutic use, according to Martin. He added that Cas14 is the smallest CRISPR enzyme identified to date, giving it a delivery advantage for therapeutic applications.
The company has not disclosed any therapeutic programs.
It also has rights to Cas12 and Cas13 enzymes, which have collateral cleavage effects. Cas12 targets double-stranded DNA, while Cas13 targets single-stranded RNA. The company also has a discovery pipeline and is “continuously expanding the toolbox,” said Martin.
“The advantage of having different enzymes is that we can multiplex in one test. We can look for different targets in RNA, DNA and ssDNA in a single reaction.”
Financial terms of the Cas14 deal were not disclosed.