Intracellular delivery of monoclonal antibodies.
With some exceptions, antibodies do not have the ability to penetrate cell membranes and act intracellularly. Their usefulness in research and medicine would be considerably enhanced if they had the intrinsic ability to act on intracellular targets. We report here that covalently linking poly-L-arginine (average molecular weight 10750, ca. 68 residues) to the oligosaccharide moiety of the CH2 region of an immunoglobulin makes possible penetration into the cytoplasm and, and in some cases into the nucleus of cells. We demonstrate this with five antibodies and seven cell lines. Retention of specificity is demonstrated by ELISA with an anti-HIV Gag antibody and intracellularly with a monoclonal anti-tubulin antibody. As the antibodies are covalently modified, they have the potential to be used in intact animals.
Chen
Bi-Xing
BX
Department of Microbiology, Columbia University, 701 West 168 Street, NY, New York 10032, USA.
Erlanger
Bernard F
BF
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001693:Biological Transport, Active; D002460:Cell Line; D015683:Gene Products, gag; D015483:HIV Antibodies / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology; D051379:Mice; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
D000911:Antibodies, Monoclonal; D015683:Gene Products, gag; D015483:HIV Antibodies; D010455:Peptides; C015462:polyarginine