A LIPIDATED ANTI-TAT ANTIBODY ENTERS LIVING CELLS AND BLOCKS HIV-1 VIRAL REPLICATION

We have developed a chemical modification of antibodies, lipidation, w hich enables their intracellular delivery into living cells. Intracell ular localization of lipidated antibodies was demonstrated by confocal microscopy and by measuring cellular uptake of I-125-labeled lipidate d antibodies. Functionally, a lipidated monoclonal antibody directed a gainst the Tat protein from human immunodeficiency virus type 1 (HIV-1 ) inhibited viral replication of several HIV-1 isolates by similar to 85% as shown by increased viability of infected cells and decreased re verse transcriptase activity. The antibody in its native form had no s uch effect. These data show that lipidated antibodies can reach and fu nctionally inhibit intracellular targets. Lipidation may help to facil itate the development of intracellular immunotherapy for AIDS.