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An Army of 5,000 Mutant Mice Helps MRC Spinoff Etiologics Take Drug Research by Storm

NEW YORK, Dec. 6 - A freezer full of mouse sperm might not seem like the strongest foundation on which to build a new company.


But Etiologics, a new spin-off from the mammalian genetics lab of the UK's Medical Research Council, expects that its massive reservoir of rodent deposits will make it an irresistible partner for pharmaceutical companies.


That's because the mice are no ordinary donors. Each has been modified through ENU mutagenesis, a chemical process that induces single-point mutations in DNA. During the past five years, MRC's mouse-genomics program has laboriously generated, screened, and banked thousands of these unique mice in the hopes of using them as models for complex human diseases.


By next spring, Etiologics will put this library on the market, according to newly hired CEO Chris Ashton. Under an exclusive commercialization deal with the MRC, the new company will offer researchers a selection from more than 5,000 genetically modified mice. The level of precision offered by this mutagenic process, says Ashton, gives drug-company customers the ability to validate targets and generate biological models for poorly understood diseases.


Pharma companies looking for disease models can provide their lists of genes to Etiologics, which will screen its archive for a mouse strain with a relevant mutation. If there's a hit, the strain can be reconstituted by impregnating a  purebred mouse with the mutated sperm and screening the offspring. Pharmaceutical researchers can then use the model mouse as both proof of the link between gene and disease and as a biological model in drug development.


"What's fantastic here is if you use purebred strains, the only difference is the single SNP you introduce," says Ashton. "You don't mine through to find the needle in the haystack. You have an irrefutable link."


This technique is superior to knockout methods, he says, because it is more subtle. Rather than prevent a gene from functioning altogether, this mutagenesis technique modifies gene activity in a way that may be more similar to the gene alterations in normal biological diversity.


"Disease is often not about complete loss of a gene, but about subtler mutations in a gene," says Ashton. "Also, human disease is often due to mutations in multiple genes. The nice thing about this is [through breeding or additional rounds of mutagenesis] you can create allele series--different mutations in different genes or more than one in the same."


GlaxoSmithKline initially backed this effort at the MRC with a 2-year, 2-million-pound collaborative agreement that helped develop the phenotypic screening and cryogenic techniques needed for this large-scale project. Interest from other pharmaceutical companies in the program drove the decision to create the spin-off, says Ashton.


Etiologics, which was formally launched in October, now has about 12 staff at facilities in MRC's Harwell campus. "We're the shop window for the entire [Mouse Genome] center here," says Ashton.


The company also plans to carry out its own drug research to find new treatments for type 2 diabetes and chronic obstructive pulmonary disease.

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