For the past five years, Emory University’s Dr. Chris Raymond has been using genomic technology designed by MilliporeSigma especially for his lab to find, remove, and replace genes in mice. This popular method of editing genes, called CRISPR, acts as genetic scissors which can be used to remove or replace an existing gene, switch a gene on or off, or insert a new gene with unprecedented accuracy. It tells Dr. Raymond whether a genetic change has potential to cause (or cure) a certain disease in mice.
Dr. Raymond, director of the Mouse Transgenic & Gene Targeting Core at Emory’s School of Medicine, has embraced MilliporeSigma’s CRISPR technology to generate mouse models of human disease. These models are then given to researchers studying new therapies for a broad range of human illnesses, from neurodegenerative diseases to cancer.
Dr. Raymond is a participant of MilliporeSigma’s CRISPR Core Partnership Program — the only CRISPR collaboration program of its kind. It is a network of commercial and research scientists that brings together the top CRISPR academic and commercial institutions in the world to share intellectual resources. The program provides participants access to MilliporeSigma’s dedicated technical support, prestigious network of experts, the strongest collection of intellectual property in the life science industry and access to the latest CRISPR technologies.
MilliporeSigma, an early adopter of genome-editing technology, has 16 years’ experience in genome editing spanning from discovery to manufacturing — more than any other company.
MilliporeSigma was the first to market with genome-editing technology and was the first to offer custom molecules globally for genome editing. The company’s early work (around 2008) was based on zinc finger nuclease technology (ZFNs), which the company has been developing and distributing to scientists globally ever since. Most recently, MilliporeSigma also manufactured the world’s first arrayed CRISPR library covering the entire human genome in partnership with the Wellcome Trust Sanger Institute, accelerating cures for diseases by allowing researchers to explore more questions about the root causes of disease. Going back even further (2005), the company was the first to offer custom RNA-guided biomolecules (TargeTron®) for genome editing in prokaryotes, leading to more options for therapeutic research in bacterial species which lacked genetic tools.
“There’s a long history that MilliporeSigma has with CRISPR technology, and we get to have a team at MilliporeSigma on call for us whenever we need it,” Dr. Raymond said of the partnership, adding that he does not need to hire someone who is dedicated to CRISPR. “There is nothing else out there that provides these types of services.”
At any one time, Emory University has about a dozen CRISPR-based mouse model projects underway. Dr. Raymond tells his MilliporeSigma partner what gene he wants to target in mice, and then the company makes a CRISPR that targets that specific gene. MilliporeSigma validates that the CRISPR works on mouse cells in its own labs, and then sends the working CRISPRs to Dr. Raymond. At Emory, Dr. Raymond’s lab injects the CRISPRs into single-cell fertilized mouse embryos, and these embryos are then implanted into surrogate female mice. Once born, the offspring are screened to determine which animals carry the edited gene.
The process of generating animal disease models is laborious and expensive requiring lots of lab space, specialized equipment, technical personnel, veterinary staff, etc. So, when MilliporeSigma delivers in vitro (taking place in a test tube, or otherwise outside of a living organism) validated CRISPRs to the customer, the risk of failure in vivo (in a living organism) is reduced.
“The gain is really the efficiency — to be able to successfully generate the models quickly and cost-effectively,” Dr. Raymond said.
MilliporeSigma offers a broad portfolio of products for the use of CRISPR technology, including ZFNs and all reagents needed for genome editing. The company regularly develops and licenses novel technology, including proxy-CRISPR, which allows scientists to access parts of the genome that were previously difficult to cut or inaccessible. By bringing more specificity to genome editing, MilliporeSigma minimizes the risk of off-target events, bringing the industry a step closer to personalized treatments.
Advancing technologies requires collaboration, and MilliporeSigma believes that no one person or organization can do it alone. The company has more strategic collaborations than any other in the industry, and works with more than 40 top pharmaceutical companies, researchers and academic institutions, including Sanger Wellcome Trust and Broad Institute.
MilliporeSigma recognizes the potential benefits of conducting properly defined research with genome editing because of the breakthrough therapeutic potential. Therefore, MilliporeSigma supports research with genome editing under careful consideration of ethical and legal standards. MilliporeSigma’s parent company, Merck KGaA, Darmstadt, Germany, has established a Bioethics Advisory Panel to provide guidance for research in which its businesses are involved, including research on or using genome editing.
The relationship with Emory is just one example of how MilliporeSigma is collaborating with the global scientific community to solve the toughest problems in life science.
Says Dr. Raymond, “Our good reputation and success has come from our partnership with MilliporeSigma.”