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Editas Licenses Engineered Cas9 Variants From MGH

NEW YORK (GenomeWeb) – Editas Medicine has signed an exclusive license agreement with Massachusetts General Hospital for CRISPR/Cas9 genome editing technology that purports to lower off-target effects and increase the number of available targets.  

Under the terms of the agreement, Cambridge, Massachusetts-based Editas will gain the rights to use engineered Cas9 variants developed in the lab of MGH scientist and Editas Cofounder Keith Joung. The Cas9 variants include nucleases engineered for higher specificity and fewer off-target edits — dubbed "high-fidelity" Cas9s — as well as Cas9s designed to allow CRISPR editing at more sites in the genome.

"Keith Joung and his MGH team have done tremendous work in creating these novel, engineered forms of Cas9," Editas CEO Katrine Bosley said in a statement. "These advancements align fully with our highly differentiated genome-editing platform." 

The workhorse of the CRISPR/Cas9 field has been the Cas9 enzyme from Streptococcus pyogenes (SpCas9). For the enzyme to cleave DNA, its target sequence (provided by the guide RNA) must abut a short sequence called a protospacer-adjacent motif (PAM). For SpCas9, the canonical PAM is NGG. As reported by GenomeWeb, Joung's lab has engineered new Cas9 variants that appear to reduce off-target effects below the current level of detection as well as other variants that recognize different PAMs. These non-canonical PAMs would increase the number of target sites available for genome editing. 

Massachusetts Institute of Technology scientist and Editas Cofounder Feng Zhang has also developed highly specific Cas9 enzymes, dubbed "enhanced SpCas9s."

According to a study published by Joung's lab in January in Nature, high-fidelity Cas9s contain mutations at four amino acid residues predicted to be in contact with the phosphate backbone of DNA.

This agreement marks a continued relationship between Editas and MGH — in December 2014, the company signed a licensing agreement with the hospital covering CRISPR/Cas9 technology developed by Joung for human and veterinary therapeutic use.