Document 0233
 DOCN  M9550233
 TI    Transfer of an anti-HIV-1 ribozyme gene into primary human lymphocytes.
 DT    9505
 AU    Leavitt MC; Yu M; Yamada O; Kraus G; Looney D; Poeschla E; Wong-Staal F;
       Department of Medicine, University of California, San Diego, La; Jolla
       92093-0665.
 SO    Hum Gene Ther. 1994 Sep;5(9):1115-20. Unique Identifier : AIDSLINE
       MED/95134789
 AB    We reported previously that human CD4+ T cell lines stably expressing a
       hairpin ribozyme targeted to the human immunodeficiency virus type 1
       (HIV-1) U5 leader sequence were resistant to challenge with diverse
       HIV-1 viral clones and clinical isolates (Yamada et al., 1994). To
       simulate more closely the in vivo infection process for investigations
       of anti-HIV-1 ribozyme gene therapy, we developed a system to transfer
       this ribozyme gene into freshly isolated human peripheral blood
       lymphocytes (PBLs) using a murine retrovirus vector. Following
       transduction and G418 selection, human PBLs from multiple donors
       expressed the ribozyme and resisted challenge by HIV-1 viral clones and
       clinical isolates, while control vector-transduced PBLs remained fully
       permissive for HIV-1 infection. No inhibition of an HIV-2 clone lacking
       the target was seen in ribozyme-expressing PBLs. Ribozyme expression had
       no effect on viability or proliferation kinetics of the primary
       lymphocytes. This study is the first demonstration in primary human T
       cells of resistance to HIV-1 infection conferred by gene transfer. A
       human clinical trial is in development to test further the safety and
       efficacy of this ribozyme in PBLs of HIV-1-infected patients in vivo.
 DE    Base Sequence  Cells, Cultured  Comparative Study  Drug
       Resistance/GENETICS  *Gene Transfer  Genetic Vectors
       Gentamicins/PHARMACOLOGY  Human  HIV-1/*GENETICS/PHYSIOLOGY
       HIV-2/PHYSIOLOGY  Immunity, Natural  *Lymphocytes/VIROLOGY  Molecular
       Sequence Data  Recombinant Fusion Proteins/BIOSYNTHESIS  RNA Polymerase
       III/METABOLISM  RNA, Catalytic/BIOSYNTHESIS/*GENETICS  Selection
       (Genetics)  *Virus Replication  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).