A lipidated anti-Tat antibody enters living cells and blocks HIV-1 viral replication.
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 approximately 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.
Cruikshank
W W
WW
Pulmonary Center, Boston University School of Medicine, Massachusetts, U.S.A.
Doctrow
S R
SR
Falvo
M S
MS
Huffman
K
K
Maciaszek
J
J
Viglianti
G
G
Raina
J
J
Kornfeld
H
H
Malfroy
B
B
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology; D001692:Biological Transport; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D015696:Gene Products, tat / Q000276:immunology*; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D015483:HIV Antibodies / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016655:HIV Core Protein p24 / Q000032:analysis; D054303:HIV Reverse Transcriptase / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology; D008856:Microscopy, Fluorescence; D017735:Virus Latency / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
D000911:Antibodies, Monoclonal; D015696:Gene Products, tat; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D007074:Immunoglobulin G; D008074:Lipoproteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D054303:HIV Reverse Transcriptase; D005998:Glycine