Document 0877
 DOCN  M9540877
 TI    In vitro and in vivo characterization of a second functional hairpin
       ribozyme against HIV-1.
 DT    9504
 AU    Yu M; Poeschla E; Yamada O; Degrandis P; Leavitt MC; Heusch M; Yees JK;
       Wong-Staal F; Hampel A; Department of Biology, University of California
       at San Diego, La; Jolla 92093-0665.
 SO    Virology. 1995 Jan 10;206(1):381-6. Unique Identifier : AIDSLINE
       MED/95133172
 AB    We have constructed a hairpin ribozyme targeted to cleave a conserved
       sequence in the HIV-1 pol gene. The ribozyme was modified to include a
       structure-stabilizing tetraloop. In vitro studies revealed a cleavage
       efficiency unprecedented for hairpin ribozymes (Kcat/Km = 75 min-1
       microM-1). Stable retroviral vector transduction of this ribozyme gene
       in T-cell lines resulted in long-term ribozyme expression. As compared
       to control vector transduced T-cells, the pol ribozyme-transduced cells
       exhibited significant inhibition of different strains of HIV-1 virus
       production; this protection was greater when ribozyme expression was
       driven from an internal pol III promoter (adenovirus VA1) than when
       driven by a pol II promoter (the MMLV LTR). These results further
       demonstrate the potential of hairpin ribozymes as anti-HIV gene therapy
       agents and suggest possibilities for employing combinations of
       independently targeted hairpin ribozymes.
 DE    Base Sequence  Cell Line  Gene Products, pol/*GENETICS/METABOLISM  Human
       Hydrolysis  HIV-1/GENETICS/*METABOLISM/PHYSIOLOGY  Kinetics  Molecular
       Sequence Data  RNA, Catalytic/*METABOLISM/PHARMACOLOGY  RNA,
       Viral/*METABOLISM  Support, U.S. Gov't, P.H.S.  T-Lymphocytes/ENZYMOLOGY
       Virus Replication/DRUG EFFECTS  JOURNAL ARTICLE

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