Expansion of HSC for rescue in biodefense applications

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DESCRIPTION (provided by applicant): Myeloablation is the damage that occurs to the bone marrow as a result of radiological or chemical exposure whether therapeutically administered or accidental, that, if left untreated, results in hematopoietic failure and death. Within the bone marrow it is the rare population of self-renewing hematopoietic stem cells (HSC) that is responsible for the generation and lifelong maintenance of the entire blood system. Hematopoietic cell transplants (HCT) are widely used clinically to allow cancer patients to survive otherwise lethal doses of chemotherapy and radiation. Thus, it is the HSC that reconstitutes the blood system and rescues HCT recipients from the otherwise lethal preparative regimen. It is this ability of the HSC that also makes it the only cell capable of rescuing those exposed to lethal doses of ionizing radiation resulting from a widespread radiological or chemical emergency. In the case of such an event, standard HCT protocols would not be applicable in a suitable timeframe or scale to be of significant medical benefit. In the current environment of increasing potential of radiological emergencies due to terrorism or other political instabilities, a method of expanding human HSCs ex vivo that can be then be stored for future use, will have incredible impact on our (nation's) ability to save the lives of both civilians and military personnel exposed to such a radiological event. It is the aim of this proposal is to produce a pre-clinical system based on Cellerant's proprietary HSC expansion technology. This technology entails the transient modification of purified HSC by adenoviral transduction to express genes that result in their ex vivo expansion. After expansion of the HSCs, the nonintegrated genetic material is removed via redundant deletion and selection procedures to result in a rigorously safe, efficacious, and easily administered treatment for exposure to life-threatening doses of ionizing radiation or chemical agents.