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.
|Titolo:||A monoclonal antibody extends the half-life of an anti-HIV oligodeoxynucleotide and targets it to CD4+ cells|
BALSARI, ANDREA (Ultimo)
|Parole Chiave:||Animals; Exodeoxyribonucleases; Oligonucleotides, Antisense; Humans; Mice; Genome, Viral; Mice, Inbred BALB C; Antiviral Agents; CD4-Positive T-Lymphocytes; Antibodies, Monoclonal; Mice, Inbred Strains; Base Sequence; Half-Life; Antigens, CD4; Molecular Sequence Data; HIV; Cell Line; Female|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||25-nov-1995|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/nar/23.22.4603|
|Appare nelle tipologie:||01 - Articolo su periodico|