       Document 0696
 DOCN  M9550696
 TI    Reduction in replication of the human immunodeficiency virus type 1 in
       human T cell lines by polymerase III-driven transcription of chimeric
       tRNA-antisense RNA genes.
 DT    9505
 AU    Junker U; Rittner K; Homann M; Bevec D; Bohnlein E; Sczakiel G;
       VIRCC-LSGT, Wien, Austria.
 SO    Antisense Res Dev. 1994 Fall;4(3):165-72. Unique Identifier : AIDSLINE
       MED/95152262
 AB    Inhibition of human immunodeficiency virus type 1 (HIV-1) replication
       was demonstrated by using tat- and rev-directed antisense
       oligoribonucleotides 68 and 69 nucleotides in length. In this study,
       human T-lymphoid cells were transduced with a murine amphotropic
       retroviral vector containing a polymerase III-driven chimeric gene
       consisting of the human tRNA(imet) sequence and the short tat- and
       rev-directed antisense sequences that had been shown before to inhibit
       HIV-1 replication. Pools of transduced, G418-resistant human T-lymphoid
       Jurkat or CEM cells showed reduced replication of HIV-1 in the presence
       of antisense-containing chimeric transcripts, but not with sense
       sequence-containing transcripts. These results demonstrate that short
       inhibitory antisense RNA transcripts can be stably expressed
       endogenously using polymerase III promoters, which can reduce
       replication of HIV-1. The approach described in this work combines the
       advantages of short and, usually, synthetic oligonucleotides with the
       stable intracellular expression of inhibitory genes for HIV-1 in target
       cells. Considering the small size of the described chimeric polymerase
       III genes, it appears feasible to combine multiple antiviral genes with
       the currently available retroviral vectors as gene delivery systems.
 DE    Cell Line  *Genes, Synthetic  Human  HIV-1/*PHYSIOLOGY  RNA Polymerase
       III/*METABOLISM  RNA, Antisense/GENETICS  RNA, Transfer/GENETICS
       Support, Non-U.S. Gov't  T-Lymphocytes/*VIROLOGY  *Transcription,
       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).

