A monoclonal antibody externds the half/life of an anti-HIV oligodeopxynucleotide4 and targets it to CD4+cells

摘要

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 ollgo 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 antl-ollgo 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 ollgodeoxynucleotides useful for the selective inhibition of HIV replication in vivo.