Circular rnas and their use in immunomodulation

Abstract

Compositions and methods of modulating an innate immune response with circular RNAs are disclosed. In particular, the disclosure relates to methods for modifying an RNA by circularization and the use of circular RNAs generated with exogenous introns to stimulate an innate immune response or circular RNAs generated with endogenous introns to prevent immune recognition of foreign RNA.

1 .- 27 . (canceled) 
     
     
         28 . A method of eliciting an immune response in a human subject, the method comprising administering to the subject a circular RNA circularized from a recombinant nucleic acid comprising: i) a 3′ portion of an exogenous non-mammalian self-splicing intron comprising a 3′ splice site, ii) a nucleic acid sequence encoding an RNA exon, and iii) a 5′ portion of the exogenous non-mammalian self-splicing intron comprising a 5′ splice site, wherein the circular RNA does not comprise m6A modification. 
     
     
         29 . The method of claim  1 , wherein the recombinant nucleic acid comprises a bacterial plasmid vector or a viral vector. 
     
     
         30 . The method of claim  1 , wherein the subject has cancer, an infectious disease, or an immunodeficiency. 
     
     
         31 . The method of claim  3 , wherein the infectious disease is caused by a pathogen selected from a virus, a bacterium, a protist, a fungus and a parasite. 
     
     
         32 . The method of claim  1 , wherein the method further comprises administering an antiviral agent, an antibiotic, an antifungal agent, an antiparasitic agent, a chemotherapeutic agent, or a vaccine. 
     
     
         33 . The method of claim  1 , wherein the circular RNA is administered before the subject is diagnosed with cancer, an infectious disease or an immunodeficiency. 
     
     
         34 . The method of claim  1 , wherein the circular RNA is administered after the subject is diagnosed with cancer, an infectious disease or an immunodeficiency. 
     
     
         35 . The method of claim  1 , wherein the circular RNA encodes an immunogenic polypeptide. 
     
     
         36 . The method of claim  8 , wherein the immunogenic polypeptide is derived from a cancer antigen, or an organism selected from the group consisting of a bacterium, a virus, a fungus, a protist, and a parasite. 
     
     
         37 . The method of claim  1 , wherein the circular RNA is administered as vaccine. 
     
     
         38 . The method of claim  1 , wherein the circular RNA is administered as adjuvant. 
     
     
         39 . The method of claim  11 , wherein the circular RNA is administered with a vaccine. 
     
     
         40 . The method of claim  12 , wherein the circular RNA enhances immune response to the vaccine. 
     
     
         41 . The method of claim  1 , wherein the circular RNA is administered as naked RNA. 
     
     
         42 . The method of claim  1 , wherein the circular RNA is administered using a lipid based carrier. 
     
     
         43 . The method of claim  15 , wherein the lipid based carrier is a nanoparticle. 
     
     
         44 . The method of claim  1 , wherein the circular RNA is administered subcutaneously, intramuscularly or trans-dermally. 
     
     
         45 . The method of claim  13 , wherein the immune response comprises a cellular immune response. 
     
     
         46 . The method of claim  18 , wherein the cellular immune response comprises immunogen-specific T cell response. 
     
     
         47 . The method of claim  13 , wherein the immune response comprises a humoral immune response. 
     
     
         48 . The method of claim  20 , wherein the humoral immune response comprises antibody response. 
     
     
         49 . The method of claim  1 , wherein the self-splicing intron is a self-splicing Group I or Group II intron.