| abstract |
Disclosed herein are methods and compositions for treating or increasing resistance HIV infection. Vectors carrying a codon-optimized CCR5delta32 gene, Hl-promoter driven CCR5shRNA and/or a triple miRNA (microRNA) intronic cassette (miR155, 19a, 30a) against HIV-1 pol, int and vpu may be packaged into virus particles. In a specific embodiment, vectors carrying the CCR5shRNA and the triple miRNA against HIV-1, pol, int and vpu without the CCR5delta32 gene are provided. Significant resistance to HIV-1 infection and envelope mediated fusion was observed in the vector-modified HOS-R5 cells that endogenously express CD4, CCR5 and CXCR4. Expression of endogenous CCR5 was inhibited more than 90% after vector CCR5shRNA gene transfer as demonstrated by flow cytometry. |