       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).

