Osel, Inc. is developing a novel live combinational microbicide by genetically modifying a H2O2-producing vaginal Lactobacillus jensenii 1153 to constitutively secrete a potent HIV-envelope targeted inhibitor, an N- terminally modified Cyanovirin-N (CV-N) (P51G), and an effective CCR5-targeted inhibitor, C1C5-RANTES. The latter is an N-terminally modified RANTES that targets the major Hiv co-receptor CCR5 with an increased antiviral and Anti-inflammatory activity. This live, self-renewing microbicide may afford an efficacious, yet inexpensive means to deliver a protein-based microbicide and address the urgent need for female-controlled approaches to block heterosexual transmission Of HIV-1. We will explore the possibility Of delivering this modified CV-N and C1C5-RANTES from a single strain Of Lactobacillus, or from a mixture Of two strains, each delivering a single inhibitor.