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Molecular Pharmacology, Vol 13, 488-495, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Cellular Uptake and Protection against Virus Infection by Polyinosinic-Polycytidylic Acid Entrapped within Phospholipid Vesicles

ERIC MAYHEW 1, DEMETRIOS PAPAHADJOPOULOS 1, JUDITH A. O’MALLEY 2, WILLIAM A. CARTER 2, and W. J. VAIL 3

1 Department of Experimental Pathology, Roswell Park Memorial Institute, Buffalo, New York 14263
2 Department of Medical Viral Oncology, Roswell Park Memorial Institute, Buffalo, New York 14263
3 Department of Microbiology, University of Guelph, Guelph, Ontario, Canada

The high molecular weight, double-stranded RNA polyinosinic-polycytidylic acid (rIn·rCn) can be entrapped by large (0.2-0.8-µm-diameter) unilamellar phospholipid vesicles. Increased cellular uptake of rIn·rCn (5-10-fold) was observed when human and mouse cells were treated with the polynucleotide entrapped within vesicles, compared with the uptake of free rIn·rCn. Both rIn, and rCn were taken up equally by cells in the entrapped form, whereas cells took up more rIn, than rCn when treated with the free polynucleotide. Vesicle-entrapped rIn·rCn enhanced interferon induction and protection against vesicular stomatitis virus (5-10-fold) by cultured human cells, compared with free rIn·rCn at initially equal external concentrations. The results suggest that phospholipid vesicles can be used to potentiate the cellular uptake of nucleic acids in a functional form.

Note:
ACKNOWLEDGMENTS We acknowledge the technical assistance of Ms. R. Lazo, Ms. K. Caruana, and Ms. J. Ciszkowski.

Submitted on August 6, 1976
Accepted on November 12, 1976






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