A monoclonal antibody extends the half-life of an anti-HIV oligodeoxynucleotide and targets it to CD4+ cells.
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.
Division of Experimental Oncology E, Istituto Nazionale Tumori, Milan, Italy.
D
D
Morelli
B
B
Pozzi
J A
JA
Maier
S
S
Ménard
M I
MI
Colnaghi
A
A
Balsari
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000998:Antiviral Agents / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D001483:Base Sequence; D015704:CD4 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D005090:Exodeoxyribonucleases / Q000097:blood / Q000302:isolation & purification; D005260:Female; D016679:Genome, Viral; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006207:Half-Life; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008815:Mice, Inbred Strains / Q000276:immunology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015704:CD4 Antigens; D016376:Oligonucleotides, Antisense; D005090:Exodeoxyribonucleases