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 speci ficity of antisense oligodeoxynucleotides (oligos). A monoclonal antib ody (MAb) was derived from mice immunised with an oligo complementary to a region (1-20) of the HIV genome. This MAb exerts a protective eff ect on the oligo from the degradation induced by plasma exonucleases i n vitro and in vivo. Moreover the anti-oligo MAb dissociates from the oligo in the presence of its complementary sequence to allow hybridiza tion of the two complementary strands. To direct the oligo to CD4(+) c ells the anti-oligo MAb was cross-linked to an anti-CD4 MAb. The heter oaggregate determines a 5-fold increase in the cellular membrane bindi ng of the oligo to CD4(+) lymphocytes. These findings suggest a new ap proach to enhancing-the therapeutic action and the target specificity of antisense oligodeoxynucleotides useful for the selective inhibition of HIV replication in vivo.