       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).

