Adeno-Associated Viral Vectors for the Delivery of Antisense RNA

Abstract

The use of antisense RNA for the inhibition of gene expression and viral pathogenesis appears promising for gene therapeutic use. We have designed a family of transducing viral vectors, based upon the noncytopathic adeno-associated virus (AAV), that encode antisense RNA targeting critical early events in the replicative cycle of targeted viruses, including human immunodeficiency virus-1 (HIV-1) and herpes simplex virus-1 (HSV-1). AAV vectors efficiently transduce cells of different types and integrate into chromosomal DNA in a stable fashion. Genes inserted into AAV vectors may be precisely designed to direct the transcription of short antisense RNA molecules since there is no transcriptional interference from the base vector. Cells expressing AAV-encoded antisense RNA show a significant reduction in the production of the cognate virus. Thus, AAV vectors may become powerful analytic and therapeutic tools for the stable introduction of transgenes including antisense genes into cells.