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TREATMENT OF HSV-2 USING A MEGANUCLEASE

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اقرأ أكثر حفظ في قائمتي
  • Publication Date:
    December 5, 2024
  • معلومة اضافية
    • Document Number:
      20240398984
    • Appl. No:
      18/670419
    • Application Filed:
      May 21, 2024
    • نبذة مختصرة :
      Described herein are compositions and methods for reducing or eliminating latent herpes simplex virus type 2 (HSV-2) from an HSV-2-infected cell, or for reducing or eliminating latent HSV-2 reactivation in an HSV-2-infected cell, leading to a viable curative approach for latent HSV-2 infection. The composition comprises a plurality of viral vectors, wherein the viral vectors comprise a sequence encoding an HSV-2-specific meganuclease. The method comprises delivering to an HSV-2-infected cell a plurality of one or more viral vectors, wherein each of the one or more viral vectors includes a sequence encoding an HSV-2-specific meganuclease.
    • Assignees:
      Fred Hutchinson Cancer Center (Seattle, WA, US)
    • Claim:
      1. A composition comprising a plurality of one or more viral vectors, wherein each of the one or more viral vectors includes a sequence encoding an HSV-2-specific meganuclease.
    • Claim:
      2. The composition of claim 1, wherein the one or more viral vectors is a self-complementary adeno-associated virus (scAAV), a single-stranded adeno-associated virus (ssAAV), or a combination thereof.
    • Claim:
      3. The composition of claim 2, wherein the ssAAV is ssAAV9, ssAAV-Dj/8, ssAAV-rh10, ssAAV8, ssAAV1, another serotype adeno-associated virus, or a combination thereof.
    • Claim:
      4. The composition of claim 2, wherein the scAAV is scAAV9, scAAV-Dj/8, scAAV-rh10, scAAV8, scAAV1, another serotype adeno-associated virus, or a combination thereof.
    • Claim:
      5. The composition of claim 1, wherein the sequence encoding the HSV-2-specific meganuclease is configured to encode an HSV-2-specific meganuclease which targets one or more HSV-2 genes essential for replication.
    • Claim:
      6. The composition of claim 1, wherein the sequence encoding the HSV-2-specific meganuclease is configured to encode an HSV-2-specific meganuclease which induces one or more DNA double strand breaks.
    • Claim:
      7. The composition of claim 1, wherein the HSV-2-specific meganuclease is configured to induce one or more DNA double strand breaks.
    • Claim:
      8. The composition of claim 1, wherein the HSV-2-specific meganuclease is configured to induce two DNA double strand breaks.
    • Claim:
      9. The composition of claim 1, wherein the HSV-2-specific meganuclease is configured to target one or more HSV-2 genes essential for replication.
    • Claim:
      10. The composition of claim 1, wherein the HSV-2-specific meganuclease comprises a sequence as set forth in SEQ ID NOs: 1-6.
    • Claim:
      11. The composition of claim 1, wherein the HSV-2-specific meganuclease comprises SEQ ID NO: 1 or 2.
    • Claim:
      12. The composition of claim 1, wherein the HSV-2-specific meganuclease comprises a sequence as set forth in SEQ ID NOs: 7-12.
    • Claim:
      13. The composition of claim 1, wherein the HSV-2-specific meganuclease is configured to target one or more sequences as set forth in SEQ ID NOs: 13 and 14.
    • Claim:
      14. The composition of claim 1, wherein the one or more viral vectors further includes a regulatory sequence.
    • Claim:
      15. The composition of claim 14, wherein the regulatory sequence comprises a sequence as set forth in SEQ ID NO: 42.
    • Claim:
      16. The composition of claim 1, wherein the plurality of one or more viral vectors comprises one to three scAAVs, wherein each scAAV is a different serotype, and wherein each scAAV includes a sequence, which is the same or different, encoding an HSV-2-specific meganuclease.
    • Claim:
      17. A pharmaceutical composition, comprising the composition of claim 1, and a pharmaceutically acceptable carrier or excipient.
    • Claim:
      18. A method of reducing or eliminating latent HSV-2 or HSV-2 reactivation in a cell, comprising administering the composition of claim 1 to the cell.
    • Claim:
      19. The method of claim 18, comprising administering the composition to a cell in an amount effective to reduce or eliminate latent HSV-2 or HSV-2 reactivation in the cell.
    • Claim:
      20. The method of claim 18, wherein the cell is a mammalian cell.
    • Claim:
      21. The method of claim 18, wherein the cell is a neuron.
    • Claim:
      22. The method of claim 18, wherein the cell is a sensory ganglia cell, an autonomic ganglia cell, or a combination thereof.
    • Claim:
      23. The method of claim 18, wherein the cell is a superior cervical ganglia cell, a trigeminal ganglia cell, a dorsal root ganglia cell, a major pelvic ganglia cell, another HSV-2 infected cell, or a combination thereof.
    • Claim:
      24. A method of reducing or eliminating latent HSV-2 or HSV-2 reactivation in a subject, comprising administering to the subject the composition of claim 1 in an amount effective to reduce or eliminate latent HSV-2 or HSV-2 reactivation in the subject.
    • Claim:
      25. A method of reducing or eliminating latent HSV-2 or HSV-2 reactivation in a subject, comprising administering to the subject the pharmaceutical composition of claim 17.
    • Claim:
      26. The method of claim 24, wherein the administering is by a subcutaneous injection or intramuscular injection.
    • Claim:
      27. The method of claim 24, wherein the subject is a mammal.
    • Claim:
      28. The method of claim 24, wherein the subject is a human.
    • Current International Class:
      61; 61; 61; 61; 12; 12
    • الرقم المعرف:
      edspap.20240398984