title: Isolation of efficient antivirals: genetic suppressor elements against HIV-1.
abstract: 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.
authors.affiliation: Ingenex Inc, Menlo Park, CA, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Dunn
authors.forename: S W
authors.initials: SW
authors.lastname: Park
authors.forename: V
authors.initials: V
authors.lastname: Sharma
authors.forename: G
authors.initials: G
authors.lastname: Raghu
authors.forename: J M
authors.initials: JM
authors.lastname: Simone
authors.forename: R
authors.initials: R
authors.lastname: Tavassoli
authors.forename: L M
authors.initials: LM
authors.lastname: Young
authors.forename: M A
authors.initials: MA
authors.lastname: Ortega
authors.forename: C H
authors.initials: CH
authors.lastname: Pan
authors.forename: G J
authors.initials: GJ
authors.lastname: Alegre
authors.forename: I B
authors.initials: IB
authors.lastname: Roninson
authors.forename: G
authors.initials: G
authors.lastname: Lipkina
authors.forename: A
authors.initials: A
authors.lastname: Dayn
authors.forename: T A
authors.initials: TA
authors.lastname: Holzmayer
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D000998:Antiviral Agents; D005434:Flow Cytometry; D015723:Gene Library; D016153:Genes, Suppressor; D015316:Genetic Therapy / Q000379:methods*; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics*; D006801:Humans
chemical_list: D000998:Antiviral Agents