Antisense Inhibition Of Fungal Growth

Immunocompromised patients provide perhaps the greatest challenge to modern health care; these patients are susceptible to infections by organisms that are normally harmless commensals. Treatment of fungal infections is difficult due to a lack of effective antifungal antibiotics. Even after 29 years of use, Amphotericin is still the drug of choice to treat systemic fungal infections; however, amphotericin is very toxic to human cells. Other antifungal agents are limited by either a narrow spectrum of activity or by toxicity or both. One striking difference between fungal and human cells is that fungal cells are encased in a wall which protects them a hostile external environment. Human pathogenic fungi contain chitin, (1-3)-beta-glucan, other glucans, peptides, and lipids as essential components of cell walls. All available information indicates that (1-3)-beta-glucan synthase activity is very important for fungal cell-wall assembly. We will form antisense constructs of a gene that codes for an essential component of beta(1,3)glucan synthase activity. We will transform fungal cells with antisense constructs and determine the effect of expression of antisense RNA on enzyme activity and fungal growth. We expect that antisense oligonucleotides may be important, novel therapeutic agents directed specifically against fungi.