Methods related to immunostimulatory nucleic acid-induced interferon
First Claim
1. A chimeric nucleic acid comprising at least two immunostimulatory nucleic acids selected from the group consisting of CpG nucleic acids, T-rich nucleic acids, and poly-G nucleic acids, wherein at least one of the at least two immunostimulatory nucleic acids induces production of interferon alpha (IFN-α
- ) from human peripheral blood mononuclear cells and has the sequence set forth byggGGGACGATCGTCgggggG (SEQ ID NO;
7),wherein each lower case letter represents phosphorothioate linkage and each upper case letter indicates a phosphodiester linkage, and wherein at least one immunostimulatory nucleic acid is an oligonucleotide comprising a diol at either or both termini.
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Abstract
Methods and compositions are provided for extending the clinical utility of IFN-α in the treatment of a variety of viral and proliferative disorders. Among other aspects, the invention provides methods which increase the efficacy of IFN-α treatment and reduce IFN-α treatment-related side effects. In addition, methods are provided for supporting the survival and for activating natural interferon producing cells (IPCs) in vitro without exogenous IL-3 or GM-CSF. The invention is based on the discovery that certain CpG and non-CpG ISNAs promote survival and stimulation of IPCs.
225 Citations
9 Claims
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1. A chimeric nucleic acid comprising at least two immunostimulatory nucleic acids selected from the group consisting of CpG nucleic acids, T-rich nucleic acids, and poly-G nucleic acids, wherein at least one of the at least two immunostimulatory nucleic acids induces production of interferon alpha (IFN-α
- ) from human peripheral blood mononuclear cells and has the sequence set forth by
ggGGGACGATCGTCgggggG (SEQ ID NO;
7),wherein each lower case letter represents phosphorothioate linkage and each upper case letter indicates a phosphodiester linkage, and wherein at least one immunostimulatory nucleic acid is an oligonucleotide comprising a diol at either or both termini. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
- ) from human peripheral blood mononuclear cells and has the sequence set forth by
Specification