Recombinetics, Inc. — Department of Health and Human Services SBIR Phase I: NHLBI

Description

DESCRIPTION provided by applicant Immunodeficient rodents has revolutionized the study of regenerative medicine and cancer to date no analogous large animals with T B and NK cell deficiency are available Weandapos ve used our novel multiplex gene editing platform to knockout each allele of two genes Recombination Activating Gene RAG and Interleukin Receptor Gamma IL Rg to establish RG KO cell lines This will dramatically reducing the time and cost associated with breeding individual genetic mutations into pigs In addition we propose to restore the immune systems in RG KO pig by blastocyst complementation and cord blood transplantation The restored immune function in these RG KO swine will enable breeding animals to be maintained in standard housing with little risk of illness or death due to infection In addition breeding between chimeric immune restored RG KOandapos s has nearly a fold advantage over intercross of between heterozygous animals This innovative method for establishment and breeding of immunodeficient provides a unique sustainable supply of animals for research in regenerative medicine xenogenic organ tissue production and cancer using a large animal which is anatomically and physiologically similar to humans This project will also establish a platform for the creation of a pig with a human immune system that would have profound impacts on the development and testing of novel therapeutics transplantation rejection studies and vaccine development PUBLIC HEALTH RELEVANCE This SBIR proposes to develop an immunodeficient pig which could be propagated in standard housing with little risk of infection This novel model would allow the study of cancer regenerative medicine and xenogeneic organ tissue production Additionally this animal would serve as a platform to make a humanized pig in which the animal would have the components of a human immune system and would allow for further studies of therapeutics transplantation rejection and vaccine development