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MUTANT OF ADENO-ASSOCIATED VIRUS (AAV) CAPSID PROTEIN

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  • Publication Date:
    August 12, 2021
  • معلومة اضافية
    • Document Number:
      20210246173
    • Appl. No:
      17/244106
    • Application Filed:
      April 29, 2021
    • نبذة مختصرة :
      The present invention provides: a mutant of adeno-associated virus (AAV) capsid protein, which contains at least one amino acid substitution in PLA2 domain when compared with the amino acid sequence for wild-type AAV capsid protein; a nucleic acid encoding the mutant; a cell containing the nucleic acid; a method for producing a recombinant AAV particle, comprising a step of culturing the cell to produce the recombinant AAV particle; a recombinant AAV particle containing the mutant; a composition containing the recombinant AAV particle; and a method for transferring a gene into a target cell, comprising a step of bringing the recombinant AAV particle into contact with the target cell.
    • Assignees:
      NIPPON MEDICAL SCHOOL FOUNDATION (Tokyo, JP), NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY (Tokyo, JP), TAKARA BIO INC. (Shiga, JP)
    • Claim:
      1-11. (canceled)
    • Claim:
      12. A mutant of an adeno-associated virus (AAV) capsid protein, comprising one or more amino acid replacements in a PLA2 domain as compared with the amino acid sequence of a wild-type AAV capsid protein, wherein the mutant is a mutant of AAV other than AAV2, and wherein the one or more amino acid replacements comprise an amino acid replacement at a position corresponding to position 68 in the amino acid sequence of wild-type AAV2 VP1 capsid protein shown by SEQ ID NO:2.
    • Claim:
      13. The mutant of an AAV capsid protein according to claim 12, wherein the one or more amino acid replacements comprise an amino acid replacement by valine at a position corresponding to position 68 in the amino acid sequence of wild-type AAV2 VP1 capsid protein shown by SEQ ID NO:2.
    • Claim:
      14. The mutant of an AAV capsid protein according to claim 12, wherein the one or more amino acid replacements further comprise amino acid replacements at positions corresponding to position 3 and position 6 in the amino acid sequence of wild-type AAV2 VP1 capsid protein shown by SEQ ID NO:2.
    • Claim:
      15. The mutant of an AAV capsid protein according to claim 12, wherein the one or more amino acid replacements comprise: (a) an amino acid replacement by threonine at a position corresponding to position 3 in the amino acid sequence of wild-type AAV2 VP1 capsid protein shown by SEQ ID NO:2, (b) an amino acid replacement by histidine at a position corresponding to position 6 in the amino acid sequence of wild-type AAV2 VP1 capsid protein shown by SEQ ID NO:2, and (c) an amino acid replacement by valine at a position corresponding to position 68 in the amino acid sequence of wild-type AAV2 VP1 capsid protein shown by SEQ ID NO:2.
    • Claim:
      16. A nucleic acid encoding the mutant of an AAV capsid protein according to claim 12.
    • Claim:
      17. A cell containing the nucleic acid according to claim 16.
    • Claim:
      18. A method of producing a recombinant AAV particle, the method comprising a step of culturing the cell according to claim 17 to produce a recombinant AAV particle.
    • Claim:
      19. The method of producing a recombinant AAV particle according to claim 18, wherein the cell according to claim 17 further contains a nucleic acid encoding an AAV Rep protein, a nucleic acid encoding an adenovirus-derived element necessary for formation of an AAV particle, and a nucleic acid having a nucleotide sequence of an AAV genomic DNA.
    • Claim:
      20. A recombinant AAV particle containing the mutant of an AAV capsid protein according to claim 12.
    • Claim:
      21. A composition containing the recombinant AAV particle according to claim 20.
    • Claim:
      22. A method of introducing a gene into a target cell, the method comprising a step of bringing the recombinant AAV particle according to claim 20 into contact with a target cell.
    • Current International Class:
      07; 12; 12
    • الرقم المعرف:
      edspap.20210246173