Compositions and methods to treat herpes simplex virus infections

Abstract

Herpes simplex virus (HSV) including herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are a persistent cause of human disease with no known cure. Guided nuclease systems target specific regions of the HSV-1 and HSV-2 genomes, disrupting the virus' nucleic acid and rendering even latent viruses incapacitated.

1 . A composition for treatment of a herpes simplex virus (HSV) infection, the composition comprising a vector encoding:
 a Cas9 endonuclease; and   a guide RNA having a portion complementary to a HSV nucleic acid, the guide RNA capable of directing the Cas9 endonuclease to the HSV nucleic acid; wherein the HSV nucleic acid comprises a long unique region 9 (UL9) or a LAT intron (LATi).   
     
     
         2 . The composition of  claim 1 , wherein the HSV nucleic acid comprises a LATi. 
     
     
         3 . The composition of  claim 1 , wherein the HSV nucleic acid comprises a UL9. 
     
     
         4 . The composition of  claim 1 , wherein the composition is configured to be administered transdermally. 
     
     
         5 . The composition of  claim 1 , wherein the composition comprises a topical solution. 
     
     
         6 .- 7 . (canceled) 
     
     
         8 . The composition of  claim 1 , wherein the composition is packaged for delivery to a human patient. 
     
     
         9 . The composition of  claim 1 , wherein the portion of the guide RNA complementary to the HSV nucleic acid has no match >60% within a human genome. 
     
     
         10 . The composition of  claim 1 , wherein the vector comprises one selected from the group consisting of: retrovirus, lentivirus, adenovirus, herpesvirus, poxvirus, alphavirus, vaccinia virus, adeno-associated viruses, a plasmid, a nanoparticle, a cationic lipid, a cationic polymer, metallic nanoparticle, a nanorod, a liposome, microbubbles, a cell-penetrating peptide, and a liposphere. 
     
     
         11 . A method for treating a herpes simplex virus (HSV) infection, the method comprising:
 introducing into a cell of a host,   (i) a vector encoding a Cas9 endonuclease and a guide RNA having a portion complementary to a HSV nucleic acid;   (ii) a ribonucleoprotein that includes a Cas9 endonuclease and a guide RNA having a portion complementary to a HSV nucleic acid; or   (iii) an mRNA encoding a Cas9 endonuclease; and a guide RNA having a portion complementary to a HSV nucleic acid;   wherein the guide RNA is capable of directing the Cas9 endonuclease to the HSV nucleic acid; and   wherein the HSV nucleic acid comprises a long repeat region 2 (RL2), a UL9, or a LATi.   
     
     
         12 . The method of  claim 11 , wherein the HSV nucleic acid comprises a LATi. 
     
     
         13 . The method of  claim 11 , wherein the HSV nucleic acid comprises a UL9. 
     
     
         14 . The method of  claim 11 , further comprising transdermally administering the vector, ribonucleoprotein, or mRNA and guide RNA to the host. 
     
     
         15 . The method of  claim 14 , wherein the transdermal administration comprises applying a topical solution comprising the vector, ribonucleoprotein, or mRNA and guide RNA. 
     
     
         16 .- 17 . (canceled) 
     
     
         18 . The method of  claim 11 , wherein the host is a living human subject and the steps are performed in vivo. 
     
     
         19 . The method of  claim 11 , wherein the apportion of the guide RNA complementary to the HSV nucleic acid has no match >60% within a human genome. 
     
     
         20 . The method of  claim 11 , wherein the vector comprises one selected from the group consisting of: retrovirus, lentivirus, adenovirus, herpesvirus, poxvirus, alphavirus, vaccinia virus, adeno-associated viruses, a plasmid, a nanoparticle, a cationic lipid, a cationic polymer, metallic nanoparticle, a nanorod, a liposome, microbubbles, a cell-penetrating peptide, and a liposphere. 
     
     
         21 . A composition for treatment of a herpes simplex virus (HSV) infection, the composition comprising a ribonucleoprotein, wherein the ribonucleoprotein comprises:
 a Cas9 endonuclease; and   a guide RNA having a portion complementary to a HSV nucleic acid, the guide RNA capable of directing the Cas9 endonuclease to the HSV nucleic acid;   wherein the HSV nucleic acid comprises a RL2, a UL9, or a LATi.   
     
     
         22 . The composition of  claim 21 , wherein the HSV nucleic acid comprises a LATi. 
     
     
         23 . The composition of  claim 21 , wherein the HSV nucleic acid comprises a UL9. 
     
     
         24 . The composition of  claim 21 , wherein the composition is configured to be administered transdermally. 
     
     
         25 . The composition of  claim 21 , further comprising a pharmaceutically acceptable carrier for topical application to infected tissue. 
     
     
         26 . (canceled) 
     
     
         27 . The composition of  claim 21 , wherein the portion of the guide RNA complementary to the HSV nucleic acid has no match >60% within a human genome. 
     
     
         28 . A composition for treatment of a HSV infection, the composition comprising:
 an mRNA encoding a Cas9 endonuclease; and   a guide RNA having a portion complementary to a HSV nucleic acid, the guide RNA capable of directing the Cas9 endonuclease to the HSV nucleic acid;   wherein the HSV nucleic acid comprises a RL2, a UL9, or a LATi.   
     
     
         29 . The composition of  claim 28 , wherein the mRNA and the guide RNA are encapsulated in or complexed with a lipid nanoparticle. 
     
     
         30 . The composition of  claim 28 , wherein the composition comprises a topical solution. 
     
     
         31 . The composition of  claim 28 , wherein the portion of the guide RNA complementary to the HSV nucleic acid has no match >60% within a human genome.