Method for delivering RNA to neurons to treat herpes infections

Patent metadata

Field	Value
Publication number	US-11351273-B2
Application number	US-201716312277-A
Country	US
Kind code	B2
Filing date	Jun 21, 2017
Priority date	Jun 21, 2016
Publication date	Jun 7, 2022
Grant date	Jun 7, 2022

Abstract

Aspects of the application relate to methods and compositions for delivering therapeutic nucleic acids to neural cells or tissue in a subject. Additional aspects of the application relate to therapeutic nucleic acids, for example therapeutic ribozymes, that are useful for inhibiting viral reactivation in a subject.

First claim

What is claimed is:

1. A method of treating infection by a neurotropic virus, comprising delivering a recombinant viral vector, wherein the vector comprises a nucleic acid encoding a ribozyme that specifically binds and/or cleaves a latency-associated region transcript of a neurotropic virus, wherein the ribozyme comprises the nucleotide sequence of SEQ ID NO: 14.

2. The method of claim 1 , wherein the latency-associated region transcript comprises a LAT transcript.

3. The method of claim 1 , wherein the neurotropic virus is selected from the group consisting of human herpes simplex virus-1 (HHV-1), human herpes simplex virus-2 (HHV-2), Varicella zoster virus (HHV-3), Epstein-Barr virus (HHV-4), Cytomegalovirus (HHV-5), Roseolovirus (HHV-6), HHV-7, and Kaposi's sarcoma-associated herpesvirus (HHV-8).

4. A method of treatment of a herpes virus infection in a subject comprising administering to the subject a recombinant viral vector comprising a nucleic acid encoding a ribozyme that specifically cleaves a latency associated region transcript of the herpes virus, thereby preventing, reducing or delaying the recurrence of pathologies associated with the reactivation of latent virus, wherein the ribozyme comprises the nucleotide sequence of SEQ ID NO: 14.

5. The method of claim 4 , wherein the subject is a human subject.

6. The method of claim 1 , wherein the ribozyme specifically binds and/or cleaves two or more latency-associated region transcripts.

7. The method of claim 1 , wherein the viral vector is a single-stranded AAV (ssAAV) or a self-complementary AAV (scAAV).

8. The method of claim 7 , wherein the viral vector is encapsidated by an AAV capsid.

9. The method of claim 8 , wherein the AAV capsid is an AAV1, AAV5, AAV7, or AAV8 capsid, or a modified variant thereof.

10. The method of claim 9 , wherein the AAV capsid is an AAV8 capsid or an AAV8(Y733F) capsid.

11. A method of delivering a recombinant nucleic acid encoding a ribozyme to a neural cell in a subject, the method comprising removing and/or disrupting epithelial cells from a tissue of the subject, and contacting the tissue with a recombinant viral vector in accordance with claim 1 .

12. The method of claim 11 , wherein the step of removing epithelial cells comprises abrading an epithelial surface.

13. The method of claim 12 , wherein the epithelial surface is located on the cornea, soft tissues of the eye, lip, mouth, nose, hand, arm, vagina, rectum, or foot of the subject.

14. The method of claim 11 , wherein the viral vector is an AAV vector.

15. The method of claim 14 , wherein the AAV vector is a recombinant AAV (rAAV), a single-stranded AAV (ssAAV), a self-complementary AAV (scAAV), a wildtype AAV, or an AAV having a modified capsid.

16. The method of claim 11 , wherein the neural cell is a sensory neuron.

17. The method of claim 16 , wherein the sensory neuron is a dorsal root ganglion neuron.

18. The method of claim 11 , wherein the ribozyme-specifically binds and/or cleaves a latency-associated region transcript.

19. The method of claim 18 , wherein the ribozyme specifically binds and/or cleaves two or more latency-associated region transcripts.

Assignees

• Univ Florida
• Board Of Supervisors Of Louisiana State Univ & Agricultural & Mechanical College

Inventors

• Bloom David C
• Lewin Alfred S
• Neumann Donna M
• Watson Zachary L
• Tuli Sonal Sanjeev
• Schultz Gregory Scott

Classifications

• C12N15/861

  Adenoviral vectors · CPC title

• C12N2830/008

  cell type or tissue specific enhancer/promoter combination · CPC title

• C12N15/1133 Primary

  against herpetoviridae, e.g. HSV · CPC title

• C12N2310/121

  Hammerhead · CPC title

• C12N5/062

  Sensory transducers, e.g. photoreceptors; Sensory neurons, e.g. for hearing, taste, smell, pH, touch, temperature, pain · CPC title