development of immunodeficient rabbit models

DESCRIPTION provided by applicant Transplantation of human or animal pluripotent stem cells PSCs or their derivatives to model animals constitutes an important preclinical system to model and investigate cell survival development and differentiation in vivo and to assess the safety and efficacy of transplantation based cell therapies Immunodeficient mice are dominantly used in biomedical research as hosts for allogeneic and xenogeneic tissue grafts In this STTR project we propose to develop a large animal immunodeficient model i e the rabbits We propose to apply our expertise in CRISPR Cas mediated gene targeting to knockout Foxn Rag Il rg and Prkdc in rabbits We also propose to test the feasibility of developing inducible immunodeficient rabbits Rabbit is a useful model for regenerative medicine It has been used to study a number of human diseases that can be treated with regenerative medicine Immunodeficient rabbits if successfully developed can help develop procedures to assess the safety of stem cell therapies over clinically relevant time frames They can be potentially important research tools to facilitate long term follow up studies of immune responses xenotransplantation stem cells and cancer thus constituting a remarkable preclinical model PUBLIC HEALTH RELEVANCE Here we propose to develop immunodeficient rabbit models taking advantage of our expertise in Cas gene targeting in this species If successfully developed these animal models can help develop procedures to assess the safety of stem cell therapies over clinically relevant time frames thus constituting a remarkable preclinical model