Compositions and methods to treat herpes simplex virus infections

• US 10,117,911 B2
• Filed: 05/27/2016
• Issued: 11/06/2018
• Est. Priority Date: 05/29/2015
• Status: Active Grant

• Current Assignee: Agenovir Corporation (Vir Biotechnology, Inc.)
• Original Assignee: Agenovir Corporation (Vir Biotechnology, Inc.)
• Inventors: Quake, Stephen R., Wang, Jianbin
• Primary Examiner(s): Gill, Rachel B
• Application Number:
  US15/167,204
• Publication Number:
  US 20160346361A1
• Time in Patent Office: 893 Days
• CPC Class Codes: A61K 2039/525 Virus
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/465 acting on ester bonds (3.1), e.g. lipases, ribonucleases
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/40 bacterial
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 48/0066 Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/195 from bacteria
• CPC Class Codes: C12N 15/09 Recombinant DNA-technology
• CPC Class Codes: C12N 15/1133 against herpetoviridae, e.g. HSV
• CPC Class Codes: C12N 15/52 Genes encoding for enzymes or proenzymes
• CPC Class Codes: C12N 15/67 General methods for enhancing the expression
• CPC Class Codes: C12N 2310/20 involving clustered regularly interspaced short palindromic repeats [CRISPRs]
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: C12N 9/16 acting on ester bonds (3.1)
• CPC Class Codes: C12N 9/22 : Ribonucleases RNAses, DNAses catalytic nucleic acids C12N15/113
• CPC Class Codes: C12Y 301/00 : Hydrolases acting on ester bonds (3.1)

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.

Claims

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 an origin of replication S (oriS) region of HSV nucleic acid, the guide RNA capable of directing the Cas9 endonuclease to the region of HSV nucleic acid.

2. The composition of claim 1, wherein the composition is configured to be administered transdermally.

3. The composition of claim 1, wherein the composition comprises a topical solution.

4. The composition of claim 1, wherein the composition is packaged for delivery to a human patient.

5. The composition of claim 1, wherein the portion of the guide RNA complementary to the origin of replication S (oriS) region of HSV nucleic acid has no match >

60% within a human genome.

6. 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.

7. 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 an origin of replication S (oriS) region of HSV nucleic acid, or

(ii) a ribonucleoprotein that includes the Cas9 endonuclease and a guide RNA having a portion complementary to an origin of replication S (oriS) region of HSV nucleic acid, wherein the guide RNA is capable of directing the Cas9 endonuclease to the region of HSV nucleic acid.

8. The method of claim 7, further comprising transdermally administering the vector or ribonucleoprotein to the host.

9. The method of claim 8, wherein the transdermal administration comprises applying a topical solution comprising the vector or ribonucleoprotein.

10. The method of claim 7, wherein the host is a living human subject and the method is performed in vivo.

11. The method of claim 7, wherein the portion of the guide RNA complementary to the origin of replication S (oriS) region of HSV nucleic acid has no match >

60% within a human genome.

12. The method of claim 7, 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.

13. 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 an origin of replication S (oriS) region of HSV nucleic acid, the guide RNA capable of directing the Cas9 endonuclease to the region of HSV nucleic acid.

14. The composition of claim 13, wherein the composition is configured to be administered transdermally.

15. The composition of claim 13, further comprising a pharmaceutically acceptable carrier for topical application to infected tissue.

16. The composition of claim 13, wherein the portion of the guide RNA complementary to the origin of replication S (oriS) region of HSV nucleic acid has no match >

60% within a human genome.

17. A composition for treatment of a herpes simplex virus (HSV) infection, the composition comprising:

an mRNA encoding a Cas9 endonuclease; and

a guide RNA having a portion complementary to an origin of replication S (oriS) region of HSV nucleic acid, the guide RNA capable of directing the Cas9endonuclease to the region of HSV nucleic acid.

18. The composition of claim 17, wherein the mRNA and the guide RNA are encapsulated in or complexed with a lipid nanoparticle.

19. The composition of claim 17, wherein the composition comprises a topical solution.

20. The composition of claim 17, wherein the portion of the guide RNA complementary to the origin of replication S (oriS) region of HSV nucleic acid has no match >

60% within a human genome.

21. The composition of claim 17, wherein the mRNA and the guide RNA are encapsulated in or complexed with a lipid nanoparticle.