ADAR1 antiviral pathway
OwnerDeborah Taylor, Stephen Feinstone +2inventors
InventorsDeborah Taylor, Stephen Feinstone, Montserrat Puig, Kathleen Mihalik
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Abstract
Methods for enhancing the production of viral vaccines in cell culture are described, as are the cell cultures. These methods rely on the suppression of the levels of ADAR1 in interferon-deficient cells. The methods comprise (a) infecting a cell culture with a donor virus, wherein said cell culture is an interferon-deficient cell culture that is deficient in ADAR1 activity; (b) culturing said infected cell culture under conditions sufficient to provide efficient virus growth; and (c) harvesting the virus produced.
Claims26
A composition of matter comprising a cell culture infected with an animal virus, wherein said cell culture is an interferon-deficient cell culture that is deficient in adenosine deaminase that acts on dsRNA (ADAR1) activity.
A method for production of a viral vaccine for an animal virus comprising:
- (a) infecting a cell culture with a donor virus, wherein said cell culture is an interferon-deficient cell culture that is deficient in ADAR1 activity;
- (b) culturing said infected cell culture under conditions sufficient to provide efficient virus growth;
- and
- (c) harvesting the virus produced.
A method for determining the antiviral activity of a compound against an animal virus, said method comprising:
- (a) infecting a cell culture with animal virus, wherein said cell culture is an interferon-deficient cell culture that is deficient in ADAR1 activity;
- (b) treating said infected cell culture with said compound;
- (c) culturing said infected cell culture under conditions sufficient to provide efficient virus growth;
- and
- (d) determining the yield of virus produced.
A method for determining the antiviral activity of a compound against an animal virus, said method comprising:
- (a) infecting a susceptible host cell culture with an animal virus;
- (b) treating said infected culture with said compound;
- (c) preparing a cell extract of said treated cell culture;
- (d) exposing under infective conditions an indicator cell culture to said cell extract, wherein said indicator cell culture is an interferon-deficient cell culture that is deficient in ADAR1 activity;
- (e) culturing said exposed cell culture under conditions sufficient to provide maximum virus growth;
- and
- (f) determining the yield of virus produced.
A method for determining the antiviral activity of a compound against an animal virus, said method comprising:
- (a) treating said animal virus with said compound;
- (b) exposing under infective conditions an indicator cell culture with said treated animal virus, wherein said indicator cell culture is an interferon-deficient cell culture that is deficient in ADAR1 activity;
- (c) culturing said exposed cell culture under conditions sufficient to provide maximum virus growth;
- and
- (d) determining the yield of virus produced.
A method for detecting the presence of virus in a sample comprising:
- (a) exposing under infective conditions an indicator cell culture to said sample suspected of containing a virus, wherein said indicator cell culture is an interferon-deficient cell culture that is deficient in ADAR1 activity;
- (b) culturing said exposed cell culture under conditions sufficient to provide for maximum virus growth;
- and
- (c) analyzing said cell culture for the presence of said virus.
A combination for treating patients having infection by hepatitis C virus or another related virus for a time sufficient to eradicate detectable virus for at least 24 weeks after the end of a period of administration comprising a therapeutically effective amount of an interferon-α and a therapeutically effective amount of an ADAR1 agonist.
A method of treating patients having infection with hepatitis C or another related virus comprising administering a therapeutically effective amount of interferon-α and a therapeutically effective amount of an ADAR1 agonist for a time sufficient to eradicate detectable virus for at least 24 weeks after the end of said period of administrating.
Dependencies are inferred from the claim text.