Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
The potential for effective antisense inhibition of retroviral replication mediated by retroviral vectors.
Raven Press Ser Mol Cell Biol; 1:261-71 1992. Unique Identifier : AIDSLINE ICDB/93689044 To RY; Neiman PE; Div. of Basic Science, Fred Hutchinson Cancer Res. Center,; Seattle, WA 98104
Abstract:
Retroviruses are a class of RNA viruses that replicate through a unique life cycle involving the reverse transcription of their positive-strand RNA genomes into DNA copies. These viral DNA copies, called proviruses, are covalently integrated into the host chromosome and expressed by normal eukaryotic transcriptional and translational mechanisms. The use of antisense strategies for management of retroviral infections is reviewed, including retroviral replication and pathogenesis, experimental inhibition of retroviral replication by antisense molecules, development of vectors for potential introduction and expression of effective antisense molecules, and testing retroviral vector-mediated antisense strategies in vivo. Because retroviruses can stably integrate their genomes into the chromosomes of host cells, efforts to suppress viral disease in vivo are complicated. Strategies that effectively block the replication cycle before integration may be the best hope for an effective antisense approach. Antisense molecules have been designed to target individual viral genes as well as splice-donor and splice-acceptor sites on the RNA in order to block expression of integrated proviral genes. To block viral integration, antisense reagents can be designed to target against regions of the genomic RNA essential for the synthesis of viral DNA intermediates or viral DNA integration. The advantage of using retroviral vectors for introducing antisense molecules into target cells is based on the nature of the retroviral infection, including the fact that cells that are susceptible to pathogenic retroviruses also are likely to be susceptible to a virus-derived vector. The feasibility of using retroviral vectors to introduce antisense molecules targeted against human T-cell lymphotropic virus (HTLV)-I and HIV infections has been demonstrated. At present, evidence at the tissue culture level points toward the possibility of employing retroviral vectors to induce cellular immunity against retrovirus infection by expressing antisense RNA molecules. Target cells for such a strategy would be hematopoietic stem cells that can be removed easily from an individual, infected with antisense retroviral vectors, and then transplanted back to the same individual or a suitable recipient by the technique of marrow transplantation. (27 Refs)
Keywords: Genes, Viral Genetic Vectors Oligonucleotides, Antisense/*PHARMACOLOGY Retroviridae/GENETICS/PHYSIOLOGY Virus Replication/*DRUG EFFECTS MONOGRAPH 930330
M9331096
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
