Searching for CRISPR 2.0, Intellia spends $45M cash on an unknown Berkeley spinout
Even as two of the first generation of CRISPR companies have shown powerful results in the clinic, they’ve faced a growing threat: new technologies such as base and prime editing that can conduct more versatile and potentially safer editing.
Intellia, which last year became the first company to show CRISPR can work directly in patients, is hoping that a little-known startup can help it stay on the cutting edge. On Thursday it announced a buyout of a tiny and effectively unknown Berkeley spinout called Rewrite Therapeutics for $45 million cash and $155 million in milestones that Intellia claims can do a host of genetic edits currently limited to prime editing and a couple other technologies.
“At Intellia, we have built the industry’s broadest and deepest genome editing platform by staying at the forefront of new techniques, while also extending the capabilities of CRISPR/Cas9 editing to make precisely targeted changes to DNA,” CEO John Leonard said in a statement. Rewrite offers Intellia “new possibilities and the potential to target diseases beyond those currently being explored in our pipeline.”
Shahram Seyedin-Noor, head of Civilization Ventures — the VC that seeded Rewrite — claimed the company is a “kind of CRISPR 2.0,” the same moniker often applied to base and prime editing but with potential improvements on both.
That’s no small boast: Prime editing caused a media frenzy when Harvard professor David Liu and his postdoc Andrew Anzalone published it in October 2019. A handful of blue-chip VCs poured $315 million into a new startup focused on turning the tech into therapies.
Prime allowed researchers to manipulate DNA in ways no other system had: changing any letter of DNA into any other and making complex changes, such as large insertions and deletion.
It is also a complex and unwieldy system, difficult to work with and difficult to fit inside the viral vectors sometimes used to deliver other CRISPR systems. (Although improvements are being made.)
Seyedin-Noor claims Rewrite’s technology allows it to be snuck inside a viral vector or lipid nanoparticle, although he didn’t elaborate on how. Historically, researchers have sometimes fit CRISPR systems into viral vectors, by breaking it apart and putting it into two different vectors, but that tends to make the system less efficient.
It can also, they say, work in non-dividing cells such as those in the nervous system, where Seyedin Noor said can be difficult to get prime editing to work.
“That’s pretty large,” said Seyedin-Noor. It “adds a whole area of therapeutics that’s untouched right now.”
Liu’s lab, however, did show efficacy in neurons in their original 2019 paper. In a Nature Gene Therapy review of the field last year, two researchers, Janine Schofield and Patrick T. Harrison, noted prime editing was particularly important because it showed precise genetic substations in non-dividing cells, “albeit at low frequency.”
And for now, Rewrite’s claims are just that. Unlike Prime, Rewrite Therapeutics’ technology remains unpublished.
Its founders, however, have released earlier iterations of the work, albeit for an entirely different application.
In 2018, Rewrite co-founder and CEO Shakked Halperin and his then-advisor David Schaffer published in Nature a CRISPR-based system that allowed researchers to target a 750-letter stretch in the genome and introduce semi-random mutations at that spot. At the time, though, they demonstrated it not as a way to edit genes in patients but to hasten and refine directed evolution — a Nobel Prize-winning technique for conducting basic research and for designing useful proteins.
Intellia was quiet about how it would use the technology, but they’ve long hinted at plans beyond Cas9. Although their headline-grabbing amyloidosis trial last year and the rest of their listed pipeline uses classic Cas9, they’ve also begun designing and publicly presenting base editors.
No word yet on how they’ll use those, either.
The article has been updated to clarify language on difference between rewrite’s technology and prime editing.