Document 0487
 DOCN  M9490487
 TI    Intracellular antibodies as a new class of therapeutic molecules for
       gene therapy.
 DT    9411
 AU    Chen SY; Bagley J; Marasco WA; Dana-Farber Cancer Institute, Department
       of Pathology, Harvard; Medical School, Boston, MA 02115.
 SO    Hum Gene Ther. 1994 May;5(5):595-601. Unique Identifier : AIDSLINE
       MED/94331443
 AB    Intracellularly expressed antibodies, referred to as intrabodies can be
       designed to bind and inactivate target molecules inside cells. In our
       previous study, mammalian cells were transduced to produce an anti-gp120
       single-chain intrabody sFv105 to inactivate human immunodeficiency virus
       type-1 (HIV-1) infection. Here, an inducible expression vector was
       constructed in which the sFv105 intrabody, which reacts with the
       CD4-binding site of HIV-1 gp120, is under the control of the HIV-1 long
       terminal repeat (LTR)/promoter. The sFv105 intrabody is inducibly
       expressed after HIV-1 infection or in the presence of Tat protein and is
       retained intracellularly. A human CD4+ lymphocyte line transformed with
       the expression vector exhibits resistance to the virus-mediated
       syncytium formation and a decreased ability to support HIV-1 production.
       Surface gp120 expression is markedly reduced and surface CD4 is restored
       to normal following HIV-1 infection in the transformed lymphocytes.
       Cell-surface phenotype, replication rate, morphology, and response to
       mitogenic stimulation of the transformed cells are also normal. Thus,
       intrabodies are a new class of active molecules that may be useful for
       the gene therapy of acquired immunodeficiency virus (AIDS) and other
       diseases.
 DE    Acquired Immunodeficiency Syndrome/IMMUNOLOGY/PREVENTION &
       CONTROL/*THERAPY  Antibodies, Viral/ANALYSIS/*IMMUNOLOGY/THERAPEUTIC USE
       Cell Line, Transformed  Fluorescent Dyes  *Gene Therapy  Genetic
       Vectors/GENETICS/IMMUNOLOGY  Human  HIV Envelope Protein
       gp120/*IMMUNOLOGY  HIV-1/*IMMUNOLOGY  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  T4 Lymphocytes/*IMMUNOLOGY/MICROBIOLOGY  JOURNAL
       ARTICLE

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