Month: July 2009

Science magazine publishes tody a report by Geurts et al. describing the first successful attempt to produce gene targeted knockout rats through the use of Zinc Finger Nuclease technology, developed by Sangamo BioSciences, Inc. This strategy does not require the use of embryonic stem (ES) cells. Targeted mutations are induced by standard microinjection of DNA and RNA molecules into 1-cell rat embryos. This milestone has been achieved by a collaborative effort of academic and industrial scientists coordinated by the biotechnology company Open Monoclonal Technology, Inc. The team includes two members of ISTT, Ignacio Anegon and Séverine Ménoret, from the Transgenic Rats Common Facility at INSERM, UMR 643, CHU, Nantes, Université de Nantes, France. Ignacio Anegon has confirmed his participation, as invited speaker, at the forthcoming TT2010 meeting, to be held in Berlin, March 22-24, 2010.

In this work, OMT scientists and their collaborators have made use of zinc finger nuclease strategies to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38. The mutations are induced at high frequency (animals carry 25 to 100% disruption at the target locus) by standard microinjection of DNA or RNA molecules encoding specific Zinc Finger Nucleases. These mutations are faithfully and efficiently transmitted through the germline. Quoting the authors: “…Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.”