Compositions and Methods to Treat Latent Viral Infections

Abstract

Viral infection is a persistent cause of human disease. Guided nuclease systems target the genomes of viral infections, rendering the viruses incapacitated.

1 .- 29 . (canceled) 
     
     
         30 . A composition comprising:
 a Cas9 endonuclease or a nucleic acid encoding a Cas9 endonuclease; and   a guide RNA that targets the Cas9 endonuclease to a viral nucleic acid in vivo within a host cell thereby causing the Cas9 endonuclease to cleave the viral nucleic acid without interfering with host nucleic acid.   
     
     
         31 . The composition of  claim 30 , wherein the viral nucleic acid is a Hepatitis B virus (HBV) nucleic acid. 
     
     
         32 . The composition of  claim 30 , wherein the guide RNA is designed to cause the nuclease to cleave the viral nucleic acid within a viral replication origin, a terminal repeat, a replication factor binding site, a promoter, a coding sequence, or a repetitive region. 
     
     
         33 . The composition of  claim 30 , wherein the composition is included within or attached or conjugated to a non-viral vector comprising a nanoparticle, a cationic lipid, a cationic polymer, a metallic nanoparticle, a nanorod, a liposome, microbubbles, a cell-penetrating peptide, a liposphere, or polyethyleneglycol (PEG). 
     
     
         34 . The composition of  claim 30 , wherein the composition comprises a plurality of guide RNAs that target different sequences within the viral nucleic acid. 
     
     
         35 . The composition of  claim 31 , wherein the guide RNA targets an HBV gene encoding a reverse transcriptase, an Hbx protein, a core protein, or a PreS1 protein. 
     
     
         36 . The composition of  claim 31 , wherein the guide RNA targets a PreS1 protein. 
     
     
         37 . The composition of  claim 30 , wherein the guide RNA comprises an sgRNA. 
     
     
         38 . A method of treating a viral infection in a subject in need thereof comprising administering the composition of  claim 30  to the subject. 
     
     
         39 . A composition comprising:
 a nucleic acid encoding:
 a Cas9 endonuclease, and 
 a guide RNA that targets the Cas9 endonuclease to a viral nucleic acid thereby causing the Cas9 endonuclease to cleave the viral nucleic acid without interfering with host nucleic acid. 
   
     
     
         40 . The composition of  claim 39 , wherein the viral nucleic acid is a Hepatitis B virus (HBV) nucleic acid. 
     
     
         41 . The composition of  claim 40 , wherein the guide RNA is designed to cause the nuclease to cleave the viral nucleic acid within a viral replication origin, a terminal repeat, a replication factor binding site, a promoter, a coding sequence, or a repetitive region. 
     
     
         42 . The composition of  claim 39 , wherein the nucleic acid is provided within or is attached or conjugated to a delivery vector. 
     
     
         43 . The composition of  claim 42 , wherein the delivery vector comprises an adeno-associated virus. 
     
     
         44 . The composition of  claim 39 , wherein the delivery vector comprises a retrovirus, a lentivirus, an adenovirus, a herpesvirus, a poxvirus, an alphavirus, a vaccinia virus, a nanoparticle, a cationic lipid, a cationic polymer, a metallic nanoparticle, a nanorod, a liposome, microbubbles, a cell-penetrating peptide, a liposphere, or polyethyleneglycol (PEG). 
     
     
         45 . The composition of  claim 40 , wherein the nucleic acid further comprises a hepatic tissue-specific promoter. 
     
     
         46 . The composition of  claim 39 , wherein the nucleic acid encodes a plurality of guide RNAs that target different sequences within the viral nucleic acid. 
     
     
         47 . The composition of  claim 40 , wherein the guide RNA targets an HBV gene encoding a reverse transcriptase, an Hbx protein, a core protein, or a PreS1 protein. 
     
     
         48 . The composition of  claim 39 , wherein the guide RNA comprises an sgRNA. 
     
     
         49 . A method of treating a viral infection in a subject in need thereof comprising administering the composition of  claim 39  to the subject.