NEW YORK (GenomeWeb) – Reflecting the escalating interest in the medical potential of the gene-editing technology CRISPR, drugmaker CRISPR Therapeutics announced last week that it has secured $25 million in Series A funding, formally kicking off operations for the company whose scientific founders include two of the RNAi field's biggest names.
The company also boasts rights to intellectual property it says is key for anyone playing in the CRISPR medicines space — an asset that could prove critical as the firm looks to operate alongside another CRISPR drugs startup, Editas Medicine, that also claims access to foundational IP.
CRISPR — short for clustered regularly interspaced short palindromic repeats — was first discovered in bacteria where a short DNA sequence known as a spacer is derived from a virus and incorporated into the bacterial genome, acting as a sort of memory of the infection.
Reinfection triggers the creation of CRISPR RNA (crRNA), single-stranded RNA that is complementary to the spacer sequence. Processed into its mature form by trans-activating crRNA (tracrRNA), crRNA acts as a guide for a complex containing the nuclease Cas9, which cuts both strands of the spacer's target DNA.
The CRISPR pathway has been adapted as a tool for selective gene engineering, wherein a specially designed crRNAs/tracrRNAs duplex known as a guide RNA (gRNA) can direct Cas9 to a DNA sequence of interest, generating the double-strand breaks that cause targeted gene silencing.
Sensing the possibility of CRISPR-based drugs, healthcare investment firm Versant Ventures ponied up $25 million on its own to get CRISPR Therapeutics up and running under the guidance of its five scientific founders. Among them is the University of Massachusetts Medical School's Craig Mello, who won a Nobel Prize in 2006 along with Stanford University's Andrew Fire for their discovery of RNAi and has gone on to cofound RNAi therapeutics shop RXi Pharmaceuticals.
Notably, CRISPR Therapeutics was also cofounded by Daniel Anderson, a Massachusetts Institute of Technology investigator who has conducted extensive research on lipid-based delivery vehicles for RNAi drugs both independently and in collaboration with Alnylam Pharmaceuticals. Anderson also recently cofounded with Monsanto a company called Preceres, which is focused on developing new dsRNA-delivery techniques for agricultural applications.
Anderson's expertise is expected to play an important role in the new firm's efforts to develop its pipeline given that CRISPR therapeutics face many of the same delivery problems that have beleaguered the RNAi drugs space.
"There is no question that to get the broadest utility from CRISPR, we need to do work on delivery," Anderson told Gene Silencing News this week. But he believes that many of the lessons learned in the RNAi and antisense fields will facilitate eventual delivery solutions for CRISPR, though he pointed out that key differences exist between the three technologies.
For now, however, CRISPR Therapeutics intends to focus on indications where CRISPR intervention can be applied ex vivo so as to "keep the complexity as limited as possible," CEO Rodger Novak said.
When it comes to actual diseases that it will pursue, the company is playing its cards close to the vest for now, but Novak said that potential areas of interest include hematopoietic stem cell modification and, for proof of concept purposes, potentially diseases of the eye.
He added that by the end of the year the company plans to identify two or three disease areas on which to focus, although it may not disclose them until later.
CRISPR Therapeutics also includes as a founder Emmanuelle Charpentier, a researcher at both Hannover Medical School in Germany and Umea University in Sweden, who conducted much of the pioneering work on understanding and harnessing CRISPR.
According to Novak, the company has taken a license to the IP around Charpentier's discoveries, including a patent application filed with the World Intellectual Property Organization under the Patent Cooperation Treaty.
That application, No. 2013176772A1, is entitled "Methods and Compositions for RNA-directed Target DNA Modification and for RNA-directed Modulation of Transcription." In addition to Charpentier, that patent application lists University of California, Berkeley researcher and Editas cofounder Jennifer Doudna as a co-inventor.
Novak said that UC Berkeley licensed its rights to the IP to Caribou Biosciences, a California-based research tool developer. Editas, he added, does not have rights to the IP.
Editas does, however, have its own IP portfolio, which includes a recently issued US patent — No. 8,697,359 — which was developed by cofounder and MIT researcher Feng Zhang and exclusively licensed to the company.
Both Editas and CRISPR refer to their respective IP estates as "foundational," and Novak said that he views his company's as vital to commercializing CRISPR drugs.
"At a minimum … if people want to move ahead in this area … [they would need] some kind of license to this IP," he said. He said that outlicensing its IP is not part of CRISPR Therapeutics's strategy at the moment, but added that this could change as the field is still in its earliest stages.
Novak declined to comment on IP held by Editas or other groups, but said that he does not anticipate the field being constrained by patent issues.
"Because of the broad applicability of this technology … there will be room for more than just one or two players," he said.