Antibodies introduced into living cells with liposomes localize specifically and inhibit specific intracellular processes.
We have developed a system for efficiently packaging antibodies and other macromolecules into liposomes and then delivering the encapsulated molecules into living cells through liposome-cell fusion. Fusion is very efficient, and all cells can be demonstrated to contain liposome-delivered antibodies by staining with a fluorescent second antibody. Using lupus antibodies directed against small nuclear ribonucleoprotein components of the cell, we were able to demonstrate strong nuclear localization, while control antibodies showed a general diffuse distribution throughout the cell. Lupus antibodies directed against ribosomes, on the other hand, strongly localized in the nucleolus and the cytoplasm with very little nucleoplasmic localization. Antitubulin antibodies predominantly localized in the cytoplasm. These results show that antibodies can survive liposome packaging and can retain their ability to recognize and bind to their specific antigens in the living cell. It also indicates that the nuclear envelope does not present a barrier to the liposome-introduced antibodies in Drosophila tissue culture cells. To determine if the antibodies were capable of interfering with cellular processes in vivo, we measured the effects of liposome-introduced antiribosome antibodies on translation and antitubulin antibodies on mitosis. In both cases, there was a significant inhibition suggesting that the antibodies can be used to interfere with specific functions at specific times in vivo.
Thompson
W S
WS
Department of Biological Sciences, Dartmouth College, Hanover, NH 03755.
Gross
R H
RH
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D002469:Cell Separation; D004337:Drug Carriers; D005434:Flow Cytometry; D006801:Humans; D008081:Liposomes; D008177:Lupus Vulgaris / Q000276:immunology; D014404:Tubulin / Q000276:immunology
D000906:Antibodies; D004337:Drug Carriers; D008081:Liposomes; D014404:Tubulin