Recombinetics, Inc. — Department of Health and Human Services SBIR Phase I: 200

Description

DESCRIPTION provided by applicant Organ transplantation is routinely used to replace entire organs in patients with a variety of health issues yet there are currently more than patients waiting to receive transplants due to lack of donors and this number is rising dramatically Exogenic organ production has the potential to alleviate the lack of available organs and help patients who are in desperate need In this proposal we aim to develop a facile platform upon which human organs can be grown in a pig and demonstrate the feasibility of this by generating pig pig chimeras in which the pancreas and its associated vasculature are entirely derived from donor pig cells We will be using blastocyst complementation which has been demonstrated to work in both mouse and pig and here we will address some major issues to make this technique clinically applicable First we will assess various pluripotent cells that coud be used for donor cells to overcome the availability cost and feasibility of using pig or human ES cells and allow us to query a number of developmental genes for exogenic organ production in the pig Second we will employ Recombineticsandapos innovative and proprietary livestock gene editing techniques to quickly and easily ablate the function of multiple genes allowing the production of chimeric animals with multiple cell lineages being donor derived Specifically two genes that are necessary for the formation of the pancreas and pancreatic vasculature will be knocked out allowing for the formation of an exogenic pancreas in pigs harboring vessels that are all solely donor derived This platform will accelerate the field of exogenic organ production and meets several needs identified in the NIH Symposium for Improving Animal Models for Regenerative Medicine In follow on Phase II studies we will evaluate organogenesis in multi lineage ablated hosts after complementation with human pluripotent cells PUBLIC HEALTH RELEVANCE This SBIR aims to develop a platform upon which human organs could be grown in a pig and used for transplantation into patients This study will allow us to develop rapid and facile techniques for investigating many different developmental genes that could be ablated for the production of many different organs and tissues Here we will develop a pig model in which the pancreas and pancreatic vasculature are completely derived from the cells of a donor pig The successful completion of this study will allow us to begin human organ production in pigs which could then be applied clinically