ANTISENSE INDUCTION OF DISEASE RESISTANCE

THE GOAL OF THIS PROGRAM IS TO USE ANTISENSE, TRANSGENIC TECHNOLOGIES TO DEVELOP A MURINE HEPATITIS VIRUS (MHV)-RESISTANT STRAIN OF MICE. DURING PHASE I, RESEARCH WILL: (1) TEST THE ANTIVIRAL EFFICACY, IN TISSUE CULTURE, OFANTISENSE OLIGONUCLEOTIDES COMPLEMENTARY TO SPECIFIC REGIONSOF THE MHV GENOME; AND (2) DEVELOP PLASMID CONSTRUCTS CONTAINING SIMILAR SEQUENCES AND PRODUCE TRANSFORMANTS THAT EXPRESS THOSE SEQUENCES AS ANTISENSE RNA'S. THESE TRANSFORMANTS WILL THEN BE TESTED FOR THEIR SUSCEPTIBILITY AND RESISTANCE TO INFECTION BY MHV. THE FINDINGS OF THESE STUDIES WILL BE APPLIED IN PHASE II TO THE DEVELOPMENTOF THE PROPER STRATEGY FOR DEVELOPING HEPATITIS-RESISTANT STRAINS OF MICE. THIS WORK HAS MAJOR SIGNIFICANCE IN THREE AREAS. FIRST, BECAUSE MOUSE HEPATITIS VIRUS IS A COMMON CONTAGION IN MOUSECOLONIES, THE DEVELOPMENT OF RESISTANT STRAINS MAY HELP TO REDUCE COLONY LOSS AND COLONY MAINTENANCE COSTS. SECOND, THE RESULTS WILL ALSO HELP DEFINE THE MECHANISM OF ACTION OF THE TWO TYPES OF ANTIVIRAL ANTISENSE THERAPIES. THIS STUDY WILL REPRESENT THE FIRST COMPARISON OF THESE ANTIVIRALSTRATEGIES ON A SINGLE SYSTEM. THIRD, SHOULD THESE EFFORTS BE SUCCESSFUL IN PRODUCING MHV-RESISTANT MICE, SIMILAR PROCEDURES FOR CONTROL OF CORONAVIRUS INFECTION IN OTHER ANIMALS (CATTLE, PIGS, AND POULTRY) CAN BE EXPLORED.