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M9490487.TXT
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1994-09-19
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).