Eyeing in-vivo editing, Mammoth licenses Jennifer Doudna’s new CRISPR enzyme – Endpoints News

Eyeing in-vivo editing, Mammoth licenses Jennifer Doudna’s new CRISPR enzyme – Endpoints News

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.

“Cas14 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 CasX and has a “search en­gine” plat­form to find oth­er pro­teins.

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.

Published at Thu, 13 Aug 2020 19:31:19 +0000