THE LONG-TERM OBJECTIVE OF THIS PROJECT IS TO DEVELOP AND COMMERCIALIZE MODIFIED POLYNUCLEOTIDES AS ANTICANCER AND ANTIVIRAL DRUGS.

THE LONG-TERM OBJECTIVE OF THIS PROJECT IS TO DEVELOP AND COMMERCIALIZE MODIFIED POLYNUCLEOTIDES AS ANTICANCER AND ANTIVIRAL DRUGS. POLY(I)MERCAPTOPOLY(C) IS SUPERIOR TO THE WELL-KNOWN INTERFERON INDUCER POLY(I)POLY(C). IN ITS ANTI- PROLIFERATIVE EFFECTS AGAINST HUMAN TUMOR CELLS, AS WELL AS IN ITS INTERFERON INDUCING ACTIVITY. FURTHERMORE, POLY(I) MPC IS LESS TOXIC IN ANIMALS THAN THE UNMODIFIED POLY(I) POLY(C). THUS, THE POTENTIAL OF POLY(I)MPC AS A USEFUL ANTITUMOR AND ANTIVIRAL DRUG IS GOOD. HOWEVER, USING PRESENT TECHNOLOGY, IT COSTS $2,000 TO PRODUCE ONE GRAM OF POLY(I)MPC. A SPECIFIC AIM OF THIS GRANT APPLICATION IS TO DEVELOP A METHOD TO PRODUCE MPC, AND THUS POLY(I)MPC, LESS EXPENSIVELY, MAKING LARGER QUANTITIES OF POLY(I)MPC AFFORDABLE FOR PRECLINICAL AND CLINICAL TESTING. IT IS PROPOSED THAT THE STARTING MATERIALS, POLY(I) AND POLY(C), WILL BE PREPARED USING AN IMMOBILIZED ENZYME SYSTEM AND THATTHE THIOLATION OF POLY(C) IN A BUFFERED AQUEOUS SOLUTION WILL BE DEVELOPED AND SCALED-UP TO CUT LABOR COST. ANOTHER SPECIFIC AIM IS TO CONFIRM THE IN VIVO ANTITUMOR ACTIVITIES OF POLY(I)MPC AND OF MPC. FAVORABLE RESULTS SHOULD LEAD TO LONGER-TERM OBJECTIVES, WHICH WOULD INCLUDE DEVELOPMENT OF OTHER MERCAPTOPOLYNUCLEOTIDES, SCALE-UP AND PRODUCTION FOR BIOLOGICAL AND CLINICAL STUDIES, AND SUBSEQUENT COMMERCIALIZATION.