A Lipidated Anti-Tat Antibody Enters Living Cells and Blocks HIV-1 Viral Replication
- 1 March 1997
- journal article
- basic science
- Published by Wolters Kluwer Health in JAIDS Journal of Acquired Immune Deficiency Syndromes
- Vol. 14 (3) , 193-203
- https://doi.org/10.1097/00042560-199703010-00001
Abstract
We have developed a chemical modification of antibodies, lipidation, which enables their intracellular delivery into living cells. Intracellular localization of lipidated antibodies was demonstrated by confocal microscopy and by measuring cellular uptake of 125I-labeled lipidated antibodies. Functionally, a lipidated monoclonal antibody directed against the Tat protein from human immunodeficiency virus type 1 (HIV-1) inhibited viral replication of several HIV-1 isolates by ~85% as shown by increased viability of infected cells and decreased reverse transcriptase activity. The antibody in its native form had no such effect. These data show that lipidated antibodies can reach and functionally inhibit intracellular targets. Lipidation may help to facilitate the development of intracellular immunotherapy for AIDS.Keywords
This publication has 16 references indexed in Scilit:
- A Controlled Trial of Zidovudine in Primary Human Immunodeficiency Virus InfectionNew England Journal of Medicine, 1995
- A Comparison of Immediate with Deferred Zidovudine Therapy for Asymptomatic HIV-Infected Adults with CD4 Cell Counts of 500 or More per Cubic MillimeterNew England Journal of Medicine, 1995
- Intracellular expression of antibody fragments directed against HIV reverse transcriptase prevents HIV infection in vitroNature Medicine, 1995
- Combined intra- and extracellular immunization against human immunodeficiency virus type 1 infection with a human anti-gp120 antibody.Proceedings of the National Academy of Sciences, 1994
- Potent inhibition of human immunodeficiency virus type 1 replication by an intracellular anti-Rev single-chain antibody.Proceedings of the National Academy of Sciences, 1994
- Intracellular Antibodies as a New Class of Therapeutic Molecules for Gene TherapyHuman Gene Therapy, 1994
- Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody.Proceedings of the National Academy of Sciences, 1993
- Mutagenesis of EIAV TAT Reveals Structural Features Essential for Transcriptional Activation and TAR Element RecognitionVirology, 1993
- Present Status and Future Prospects for HIV TherapiesScience, 1993
- The Efficacy of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-Related ComplexNew England Journal of Medicine, 1987