Oligoadenylate synthetase (OAS)
The invention describes novel pharmaceutical compositions for the treatment of virus infections and cancer. The pharmaceutical compositions include mutant oligoadenylate synthetases (OAS) that have either enhanced cell permeability, reduced oxidative potential, improved antiviral activity, improved enzymatic activity, or absent enzymatic activity. The pharmaceutical compositions have improved drug properties and retain or have enhanced antiviral activity relative to their native forms. The pharmaceutical compositions further include chemically modified oligoadenylate synthetases, such chemical modifications being designed to increase serum stability and reduce immunogenicity in vivo. Such chemical modifications further increase drug stability and manufacturability in vitro. Compositions composed of more than ninety novel modifications are described. Also described are antibodies to polypeptides of the invention.
1. An isolated polynucleotide encoding an isolated polypeptide comprising an enzymatically inactive 2′,5′ oligo-adenylate synthetase (OAS) wherein the amino acid sequence of said enzymatically inactive OAS differs from native OAS protein, but said polypeptide retains antiviral activity, and wherein said polypeptide has the sequence of SEQ ID NO:1 except that alanine is at position 75 of SEQ ID NO:1 and/or position 77 of SEQ ID NO:1.