METHODS FOR IMPROVING EXPRESSION OF TRANSFECTED IMMUNOGLOBULIN GENES

THE AIM OF THIS RESEARCH PROPOSAL IS TO DEVELOP METHODS TO IMPROVE THE EXPRESSION OF TRANSFECTED IMMUNOGLOBULIN (IG) GENES. THE LONG-TERM GOAL IS TO IMPROVE THE YIELD OF GENETICALLY ENGINEERED ANTIBODIES OF THERAPEUTIC VALUE. PHASE I WILL INVESTIGATE TWO APPROACHES TO INCREASE EXPRESSION. ONE APPROACH IS TO IDENTIFY HOST MYELOMA CELLS THAT ARE MORE ACTIVE IN EXPRESSING TRANSFECTED IG GENES; THE OTHER APPROACH IS TO DEVELOP SCHEMES TO INCREASE THE NUMBER OF GENE COPIES THAT ARE EXPRESSED. PHASE II RESEARCH WILL IMPLEMENT THE FINDINGS OF PHASE I TO FORMULATE A METHODOLOGY AND SET UP EXPERIMENTS TO EXPRESS HIGH LEVELS OF GENETICALLY MODIFIED ANTIBODIES. THE RESEARCH THAT IS PROPOSED HERE COULD LEAD TO THE PRODUCTION OF GENETICALLY MODIFIED ANTIBODIES IN YIELDS COMPARABLE TO THAT OF HIGHLY PRODUCTIVE MYELOMA OR HYBRIDOMA CELL LINES. THIS WOULD THEN MAKE THE PRODUCTION OF GENETICALLY ENGINEERED ANTIBODIES A COMMERCIALLY FEASIBLE PROCESS.