Isolation of efficient antivirals : genetic suppressor elements against HIV-1

• Published in: Gene therapy Vol. 6; no. 1; pp. 130 - 137
• Main Authors: DUNN, S. J, PARK, S. W, RONINSON, I. B, LIPKINA, G, DAYN, A, HOLZMAYER, T. A, SHARMA, V, RAGHU, G, SIMONE, J. M, TAVASSOLI, R, YOUNG, L. M, ORTEGA, M. A, PAN, C.-H, ALEGRE, G. J
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 1999
• Subjects: Acquired Immunodeficiency Syndrome - therapy; AIDS/HIV; Antiviral Agents; Biological and medical sciences; Biotechnology; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Gene Library; Gene therapy; Genes, Suppressor; Genetic Therapy - methods; Genome, Viral; Health. Pharmaceutical industry; HIV-1 - genetics; Human immunodeficiency virus 1; Humans; Industrial applications and implications. Economical aspects; Human; HIV-1 virus; Retroviridae; AIDS; Gene expression; Lentivirus; Infection; Virus; Cell line; Gene; Viral disease; Antiviral; Human immunodeficiency virus; Inhibition; Gene therapy
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3300791

The development of general approaches for the isolation of efficient antivirals and the identification and validation of targets for drug screening are becoming increasingly important, due to the emergence of previously unrecognized viral diseases. The genetic suppressor element (GSE) technology is an approach based on the functional expression selection of efficient genetic inhibitors from random fragment libraries derived from a gene or genome of interest. We have applied this technology to isolate potent genetic inhibitors against HIV-1. Two strategies were used to select for GSEs that interfere with latent virus induction and productive HIV-1 infection based on the expression of intracellular and surface antigens. The selected GSEs clustered in seven narrowly defined regions of the HIV-1 genome and were found to be functionally active. These elements are potential candidates for the gene therapy of AIDS. The developed approaches can be applied to other viral pathogens, as well as for the identification of cellular genes supporting the HIV-1 life cycle.