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M9620823.TXT
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1996-02-26
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Document 0823
DOCN M9620823
TI Rapid protection against human immunodeficiency virus type 1 (HIV-1)
replication mediated by high efficiency non-retroviral delivery of genes
interfering with HIV-1 tat and gag.
DT 9602
AU Lori F; Lisziewicz J; Smythe J; Cara A; Bunnag TA; Curiel D; Gallo RC;
Laboratory of Tumor Cell Biology, National Cancer Institute,; National
Institutes of Health, Bethesda, Maryland 20892, USA.
SO Gene Ther. 1994 Jan;1(1):27-31. Unique Identifier : AIDSLINE
MED/96050916
AB Efficient transduction of inhibitory genes is a critical requirement in
the development of a gene therapy strategy against human
immunodeficiency virus type 1 (HIV-1). Commonly used systems based on
retrovirus-mediated gene delivery are characterized by low efficiency
gene transfer into the target cell. Genes were transduced in the absence
of cell selection into 60-90% of human CD4+ cells by using a novel
technique that allows high efficiency gene transfer mediated by
adenoviruses coupled with DNA-polylysine complexes. Protection of these
cells against HIV-1 acute infection was evaluated by transducing them
with three different inhibitory genes which interfere with HIV-1
replication at separate levels (polymeric Tat activation response
element [TAR] decoy, dominant-negative mutant of the gag gene and
antisense sequences of the gag gene) and subsequent challenging with
HIV-1. The polymeric TAR decoy inhibited HIV-1 replication over 95%.
Both the dominant-negative mutant and the antisense sequence of the gag
gene were less potent inhibitors than the polymeric-TAR decoy.
Combinations of either polymeric-TAR with dominant-negative mutant or
antisense of the gag gene synergistically enhanced the inhibitory
effects of the single genes. These data suggest that the combination of
a highly efficient transduction technique with effective HIV-1
inhibitory genes confers rapid protection against HIV-1 acute infection
in vitro.
DE Adenoviridae/GENETICS DNA, Recombinant/ADMINISTRATION & DOSAGE/GENETICS
Gene Therapy Gene Transfer *Genes, gag *Genes, tat Hela Cells Human
HIV-1/*GENETICS/*PHYSIOLOGY Mutation Polylysine Time Factors
*Transduction, Genetic Virus Replication/*GENETICS JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).