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Molecular Pharmacology, Vol 16, 313-323, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

The Formation of Complexes between Polynucleotides, Carboxymethylcellulose and Polylysine Which Are Anti-viral in Mice without Inducing Interferon

NOWELL STEBBING 1 and KEITH M. DAWSON 1

1 Anti-Virals Department, Searle Research Laboratories, Lane End Road, High Wycombe, Bucks, England

Poly(rI) and poly(rC) can each be wrapped with a colloidal complex of low viscosity carboxymethylcellulose and polylysine, without formation of precipitates, to form complexes containing 10 mg/ml polynucleotide material. From its resistance to ribonuclease treatment and inability to anneal to poly(rC) we conclude that the carboxymethylcellulose polylysine wrapped poly(rI) is really wrapped. Migration of wrapped poly(rI) and wrapped poly(rC) in agarose gel electrophoresis demonstrated that the negative charges of the polynucleotides were neutralized by wrapping. The double-stranded polynucleotide, poly(rI)·poly(rC), could also be wrapped by the same procedure but only to a final polynucleotide concentration of 2 mg/ml. The wrapping procedure should be effective for any polynucleotide. Mixtures of equal masses of wrapped poly(rI) and wrapped poly(rC) do not produce detectable serum interferon concentrations in mice when both polynucleotides are administered at 25 µg/mouse or less while wrapped poly(rI)·poly(rC) produces high concentrations of serum interferon. However, at equal polynucleotide doses the wrapped single-stranded polynucleotide preparations can produce the same degree of resistance to infection with encephalomyocarditis virus as wrapped poly(rI)·poly(rC).

Note:
ACKNOWLEDGMENTS We thank Dr. N. H. Carey for critical examination of the manuscript; I.J.D. Lindley for assistance with mouse experiments; Janet Witney for agarose gel analyses; and Dr. A.J. Hale for providing the research facilities that made these studies possible.

Submitted on October 3, 1978
Accepted on December 13, 1978




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Home page
 Journal of Bioactive and Compatible PolymersHome page
H. B. Levy
Review : Polynucleotides as Interferon Inducers and Immune Modulators
Journal of Bioactive and Compatible Polymers, July 1, 1986; 1(3): 348 - 385.
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