Inhibition of simian immunodeficiency virus by foamy virus vectors expressing siRNAs.
Viral vectors available for gene therapy are either inefficient or suffer from safety concerns for human applications. Foamy viruses are non-pathogenic retroviruses that offer several unique opportunities for gene transfer in various cell types from different species. In this report, we describe the use of simian foamy virus type 1 (SFV-1) vector to examine the efficacy of therapeutic genes. Hairpin short-interfering RNA (siRNA) that targets the simian immunodeficiency virus (SIV) rev/env was placed under the control of the PolIII U6 snRNA promoter for expression and screened for silencing target genes using cognate target-reporter fusions. We have identified an effective siRNA (designated R2) which reduces the rev and env gene expression by 89% and 95%, respectively. Using the simian foamy virus type 1 (SFV-1) based vector, we delivered the PolIII expressed R2 siRNA into cultured cells and challenged with SIV. The results show that the R2 siRNA is a potent inhibitor of SIV replication as determined by p27 expression and reverse transcriptase assays. Vectors based on a non-pathogenic SFV-1 vector may provide a safe and efficient alternative to currently available vectors, and the SIV model will help devise protocols for effective anti-HIV gene therapy.
Park
Jeonghae
J
Department of Pathobiology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
Nadeau
Peter
P
Zucali
James R
JR
Johnson
Calvin M
CM
Mergia
Ayalew
A
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015870:Gene Expression; D015752:Genes, env; D015757:Genes, rev; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000502:physiology; D016092:Spumavirus / Q000235:genetics*; D014779:Virus Replication
D034741:RNA, Small Interfering