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M9630080.TXT
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1996-02-27
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Document 0080
DOCN M9630080
TI A monoclonal antibody extends the half-life of an anti-HIV
oligodeoxynucleotide and targets it to CD4+ cells.
DT 9603
AU Morelli D; Pozzi B; Maier JA; Menard S; Colnaghi MI; Balsari A; Division
of Experimental Oncology E, Istituto Nazionale Tumori,; Milan, Italy.
SO Nucleic Acids Res. 1995 Nov 25;23(22):4603-7. Unique Identifier :
AIDSLINE MED/96103588
AB An approach was sought to increase the half-life and target cell
specificity of antisense oligodeoxynucleotides (oligos). A monoclonal
antibody (MAb) was derived from mice immunised with an oligo
complementary to a region (1-20) of the HIV genome. This MAb exerts a
protective effect on the oligo from the degradation induced by plasma
exonucleases in vitro and in vivo. Moreover the anti-oligo MAb
dissociates from the oligo in the presence of its complementary sequence
to allow hybridization of the two complementary strands. To direct the
oligo to CD4+ cells the anti-oligo MAb was cross-linked to an anti-CD4
MAb. The heteroaggregate determines a 5-fold increase in the cellular
membrane binding of the oligo to CD4+ lymphocytes. These findings
suggest a new approach to enhancing the therapeutic action and the
target specificity of antisense oligodeoxynucleotides useful for the
selective inhibition of HIV replication in vivo.
DE Animal Antibodies, Monoclonal/*PHARMACOLOGY Antigens, CD4/*PHYSIOLOGY
Antiviral Agents/IMMUNOLOGY/*PHARMACOLOGY/PHARMACOKINETICS Base
Sequence Cell Line CD4-Positive T-Lymphocytes/IMMUNOLOGY/*VIROLOGY
Exodeoxyribonucleases/BLOOD/ISOLATION & PURIF Female *Genome, Viral
Half-Life Human HIV/*DRUG EFFECTS/GENETICS/IMMUNOLOGY Mice Mice,
Inbred BALB C/IMMUNOLOGY Mice, Inbred Strains/IMMUNOLOGY Molecular
Sequence Data Oligonucleotides, Antisense/IMMUNOLOGY/*PHARMACOLOGY/
PHARMACOKINETICS Support, Non-U.S. Gov't JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).