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Nucleic Acids Research, 1995, Vol. 23, No. 22 4603-4607
© 1995

Articles

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

Daniele Morelli*, Barbara Pozzi, Jeanette A.M. Maier1, Sylvie Mgnard, Maria I. Colnaghi and Andrea Balsari2

Division of Experimental Oncology E, Istituto Nazionale Tumori Milan, Italy 1Department of Biomedical Sciences and Technologies Ospedale San Raffaele, Milan, Italy 2Institute of Pathology, University of Milan Milan, Italy

*To whom correspondence should be addressed

Received August 29, 1995. Accepted October 16, 1995.

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.


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