*OUR LONG TERM GOAL IS TO UTILIZE THE YEAST S.

*OUR LONG TERM GOAL IS TO UTILIZE THE YEAST S. CEREVISIAE AS A VECTOR TO SYNTHESIZE CLONED HUMAN LYSOSOMAL ENZYMES WITH A SPECIFIC OLIGOSACCHARIDE THAT WILL TARGET THE ENZYMES TO TISSUE MACROPHAGES. THIS MAY FORM THE BASIS OF A NOVEL ENZYME-REPLACEMENT THERAPY FOR SEVERAL INHERITED LYSOSOMAL STORAGE DISEASES, AS THE DUAL PROBLEMS OF EFFECTIVE TARGETING AND LARGE SCALE, LOW COST PRODUCTION OF REPLACEMENT ENZYMES WOULD BE SOLVED. HERE WE WILL UTILIZE THE YEAST ENZYME INVERTASE AS A MODEL FOR SUCH STUDIES. CERTAIN YEAST MUTANTS WITH TEMPERATURE-SENSITIVE BLOCKS IN THE SECRETION PATHWAY SHOULD ACCUMULATE INVERTASE INTRACELLULARLY WITH DEFINED ASPARAGINE-LINKED OLIGOSACCHARIDES WITH 8 OR 9 MANNOSE RESIDUES PER CHAIN. WE WILL PURIFY AND CHARACTERIZE BOTH WILD-TYPE AND MODIFIED INVERTASES, AND TEST THEIR ABILITY TO BIND TO RAT ALVEOLAR MACROPHAGE MANNOSE RECEPTORS. AS TIME PERMITS, WE WILL ALSO TEST WHETHER THEY ARE TARGETED TO HEPATIC MACRPHOPHAGES AFTER INJECTION INTO RATS.