Compositions and Methods of Delivering Treatments for Latent Viral Infections

Abstract

The invention provides delivery methods and compositions for antiviral therapeutics. Methods and compositions are provided for targeted delivery of antiviral therapeutics into cells of interest using, for example, viral vectors such as adenovirus, AAV, and replication incompetent HSV. These and other delivery systems can be used as vehicles to deliver DNA vectors encoding a nuclease or a cell-killing gene. These delivery methods can also be used to deliver naked DNA or RNA, protein products, plasmids containing a promoter that is active only in a latent viral state which drives a cell-killing gene, or other therapeutic agents.

1 - 18 . (canceled) 
     
     
         19 . A composition for treating a viral infection, the composition comprising:
 a vector that includes a gene for a Cas9 endonuclease, a sequence that encodes one or more guide RNAs that target the nuclease to nucleic acid from a genome of the Varicella-zoster virus, and a regulatory element that causes the gene for the Cas9 endonuclease to be active within a cell that is infected by the virus.   
     
     
         20 . The composition of  claim 19 , wherein the regulatory element is from a genome of the virus. 
     
     
         21 . The composition of  claim 20 , wherein the regulatory element is one selected from the group consisting of a promoter and an origin of replication. 
     
     
         22 - 29 . (canceled) 
     
     
         30 . The composition of  claim 19 , wherein the one or more guide RNAs are designed to target a regulatory element in the genome of the virus. 
     
     
         31 . (canceled) 
     
     
         32 . A composition for treating a viral infection, the composition comprising:
 a vector comprising a gene for a Cas9 endonuclease, a sequence that targets the nuclease to a genome of the Varicella-zoster virus, and a promoter that promotes transcription from the vector within cells of a specific type.   
     
     
         33 . The composition of  claim 32 , wherein the cells are nerve cells and the promoter further causes the expression of the gene selectively within the nerve cells. 
     
     
         34 . The composition of  claim 33 , wherein the promoter comprises a cytomegalovirus promoter, a Rous sarcoma virus promoter, or a platelet-derived growth factor (PGDF) promoter. 
     
     
         35 . (canceled) 
     
     
         36 . The composition of  claim 33 , wherein the sequence is designed to target a regulatory element in the genome of the virus and lacks any exact match in a human genome. 
     
     
         37 . (canceled) 
     
     
         38 . The composition of  claim 36 , wherein the sequence is within a clustered regularly interspaced short palindromic repeats (CRISPR) region within the vector, wherein the CRISPR region encodes a plurality of guide RNAs that match a plurality of targets within the genome of the virus. 
     
     
         39 . The composition of  claim 32 , wherein the promoter promotes transcription within the peripheral nervous system. 
     
     
         40 . The composition of  claim 39 , wherein the vector comprises an adenoviral vector or a rAAV-based vector.