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.
Morelli
D
D
Division of Experimental Oncology E, Istituto Nazionale Tumori, Milan, Italy.
Pozzi
B
B
Maier
J A
JA
Ménard
S
S
Colnaghi
M I
MI
Balsari
A
A
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