APOPTOSIS INTERVENTION IN CELL AND ORGAN PRESERVATION

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BioLife Technologies is a wholly owned subsidiary of Cryomedical Sciences (CMS) incorporated on March 31, 1998 under the General Corporation Law of the State of Delaware. BioLife's primary mission is to develop improved hypothermic (cold storage) solutions designed to maintain cells, tissues and organs in a near state of suspended animation at 4 degrees C. Cardioplegia, organ transplant and selected non-regulated markets have been targeted. Data presented herein demonstrate that BioLife's hypothermic solutions, the HypoThermosol (HTS) series, are better at cold-protecting kidney, heart and skin cells than is ViaSpan - a product produced by DuPont-Merck. ViaSpan currently commands the largest market share in the transplant solution business, but it has not been significantly modified since its introduction 10 years ago. More importantly, the design of ViaSpan is not based on modern molecular biology investigations. BioLife has launched an aggressive program to determine the molecular basis of cell death during extended hypothermic storage so that knowledge of these events can lead to a new generation of hypothermic solutions. DNA gels presented in this proposal demonstrate that cells cold stored for too long die by apoptosis (programmed cell death) two days after they are returned to normothermic (37 degrees C) temperatures. HTS supplemented with apoptosis inhibitors blocks this process and improves HTS's performance. CMS patent lawyers have advised BioLife Technologies that the inclusion of apoptosis inhibitors in a future generation series of FITS solutions warrants a patent application. The Specific Aims of this Phase I project are to determine if: (1) apoptosis that occurs during extreme hypothermia is best prevented when apoptosis inhibitors are added before, during and/or after the hypothermic event; (2) if hypothermia-induced apoptosis occurs to human skin, kidney, liver, lung and aortic cells; (3) activation of cell death inhibiting genes prevents hypothermia-induced apoptosis; (4) inhibition of apoptosis thought to occur during cryopreservation (-180 degrees C) also increases the efficacy of HTS cryopreservative solutions. Successful completion of this Phase I SBIR will lead to (1) improved cold storage solutions based on sound molecular biology investigations and (2) a patent protection package that will preclude any other company from developing similar cold storage solutions based on apoptosis inhibition. PROPOSED COMMERCIAL APPLICATIONS: BioLife Technologies proposes to develop solutions to be used for the hypothermic storage of cells, tissues and organs. Applications may include engineered tissues, cardioplegia and organ transport/transplant.