The Broad Institute of MIT and Harvard signed non-exclusive license agreements granting access to its intellectual property relating to the CRISPR/Cas9 gene engineering system for research purposes to GE Healthcare Life Sciences and Sigma-Aldrich, the companies said separately today.

The IP license signed with GE Healthcare Life Sciences includes the first granted patent for the use of CRISPR technology in eukaryotic cells. U.S. Patent No. 8,697,359 was assigned to the Broad Institute and MIT based on work first described in a paper published January 3, 2013, in Science. The paper’s senior author was the listed inventor on the patent, Feng Zhang, Ph.D., a Broad Institute core member.

According to GE Healthcare Life Sciences, the license granted by Broad will enable further development of the Dharmacon Edit-R Gene Engineering System, the CRISPR/Cas9-based platform launched by the company in October. The platform is designed for creating permanent and heritable gene knockouts in cells in one-to-two weeks, compared with the previous one-month timescale.

The license will enable GE Healthcare Life Sciences to incorporate the patented technologies, as well as launch additional, complementary gene editing tools, the company added.

GE Healthcare acquired Dharmacon earlier this year as part of its acquisition of Thermo Fisher Scientific’s cell culture media and sera, gene modulation technologies, and magnetic beads businesses, all for a combined $1.06 billion. Thermo Fisher Scientific agreed to sell the businesses in November 2013 as a condition of winning European Commission (EC) approval to acquire Life Technologies for $13.6 billion, plus assumption of $2.2 billion in the acquired company’s debt, a deal completed in February.

“In line with the strategy outlined at the time of acquisition in March 2014, this license is a crucial step in our further development of Dharmacon’s added-value tools and technology offerings for the bioscience research community,” Eric Roman, general manager of research and applied markets, GE Healthcare Life Sciences, said in a company statement.

Added Michael Deines, general manager of Dharmacon: “This agreement provides a strong foundation for new, differentiated gene editing products which harness the power of the CRISPR/Cas9 system, extending our existing RNAi and gene expression portfolio to encompass the broadest range of gene modulation technologies.”

Sigma-Aldrich said its agreement with the Broad Institute will enable the company to make, use, and distribute the advanced gene editing tools for applications that include the generation of modified plant and animal models, custom cell line creation and for CRISPR/Cas arrayed and pooled genetic screening.

According to Sigma-Aldrich, the agreement enables the company to pair its lentiviral manufacturing core competency and genome editing expertise with CRISPR to create next-generation screening tools, including pre-designed or customizable individual lentiviral CRISPR clones, as well as off-the-shelf or custom lentiviral CRISPR pools. The company's first off-the-shelf offering is a collection of clones targeting the human kinome, a group of genes commonly involved in cancer and development.

“Scientists who have screened with RNAi knockdown in the past can now quickly and easily validate their results with a CRISPR knockout experiment.  This represents a specific advantage for screening small molecules as potential anti-cancer therapeutics in the drug discovery workflow,” Shaf Yousaf, Sigma-Aldrich’s vp of technology and business development, said in a company statement.

Sigma-Aldrich is the exclusive distributor of the Broad Institute's complete Mission® shRNA and ORF libraries.

The agreements were disclosed less than a week after the Broad Institute became one of four top-tier institutions to exclusively license from Editas Medicine intellectual property and technology related to CRISPR/Cas9 and TALE genome editing systems developed by four of Editas’ founders—one of them Dr. Zhang—and a fifth investigator specializing in genome editing.

The GE Healthcare Life Sciences and Sigma-Aldrich agreements comes less than a month after executives of both companies spotlighted some of CRISPR’s limitations compared with RNA interference (RNAi) in interviews with GEN.

“If the ultimate goal is the creation of new drugs, RNAi may be preferable to CRISPR for validating new drug targets because small molecule drugs only reduce a gene’s function somewhat, as RNAi does, rather than knocking it out entirely, as CRISPR does,” said Shawn Shafer, Ph.D., Sigma-Aldrich’s functional genomics market segment manager.

Added Anja Smith, Ph.D., director of R&D for GE Healthcare Dharmacon: “If you were to do genome-scale arrayed screens, I would argue that the efficiency is not as high [for CRISPR] as in RNAi knockdown.”

However, Alex Amiet, senior product manager at GE Healthcare Dharmacon, told GEN that for in-depth exploration of individual genes, “CRISPR can do things that RNAi cannot do”—including creating tagged fusion proteins and introducing single-nucleotide polymorphisms (SNPs).

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