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OwnerMasakazu KURITA, Motoi KATO +7inventors
InventorsMasakazu KURITA, Motoi KATO, Qi SHEN, Yusuke HIRABAYASHI, Shogo SUGA, Keiichiro SUZUKI, Zening DU, Hironori HOJO, Hiroyuki OKADA
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[Problem] There is no gene transduction method with high efficiency and high specificity for skin, subcutaneous tissue, skin ulcer surfaces, and their constituent cells. More generally, achieving high gene transduction efficiency in vivo is challenging. Additionally, it is difficult to morphologically and functionally regenerate skin appendages and to regenerate lost peripheral tissues of the upper and lower limbs (upper arm, forearm, hand, fingers, thigh, lower leg, foot, toes). [Solution] This invention provides solutions to these challenges through a novel AAV (adeno-associated virus) capsid with high gene transduction efficiency and high specificity for skin, subcutaneous tissue, and skin ulcer surface cells, as well as a novel AAV capsid with high gene transduction efficiency and high specificity for epidermal tissue and its constituent keratinocytes. Additionally, the invention provides a novel tissue-specific promoter with high gene expression efficiency and high specificity for epidermal tissue and its constituent keratinocytes, and a pharmaceutical composition that enhances gene transduction efficiency by co-administering steroids alongside in vivo gene transduction. The invention further includes a pharmaceutical composition that promotes the regeneration, neogenesis, and functional enhancement of skin appendages through in vivo gene transduction, thereby compensating for functional impairments of skin appendages. Additionally, it provides a research and development platform for developing methods to regenerate peripheral and missing tissues of the upper and lower limbs, as well as a pharmaceutical composition for achieving tissue regeneration. Thus, the present invention provides methods for overcoming these challenges.
A non-naturally modified adeno-associated virus (AAV) capsid protein, comprising a peptide insertion relative to its corresponding parent AAV capsid protein, wherein the peptide insertion includes the amino acid sequence EPKARAP (SEQ ID NO:
A non-naturally modified adeno-associated virus (AAV) capsid protein, comprising a peptide insertion relative to the parent AAV capsid protein AAVDJ, and having an amino acid sequence selected from SEQ ID NO:
A promoter for tissue- or cell-specific expression of a target gene in mammalian cells, comprising a nucleotide sequence described in SEQ ID NO:
A promoter for tissue- or cell-specific expression of a target gene in mammalian cells, comprising a nucleotide sequence described in SEQ ID NO:
A gene transduction vector for inducing skin tissue with skin appendages from a skin ulcer surface in vivo by transducing a gene encoding at least one of DNP63A, GRHL2, TFAP2A, cMYC, LEF1, SOX2, HOXC4, HOXC9, HOXC13, JARID2, HEY1, HEY2, FOXO1, FOXD1, EGR3, MEF2C, LHX2, PRRX1, PRRX2, CREB3, ETV1, TBX6, MSX2, PRDM1, or SHH.
A gene transduction vector for inducing skin tissue with skin appendages from a skin ulcer surface in vivo by transducing a gene encoding at least one of DNP63A, GRHL2, TFAP2A, cMYC, LEF1, FOXD1, PRDM1, or SHH.
A gene transduction vector for inducing the neogenesis of skin appendages or enhancing skin appendage function in vivo by transducing a gene encoding all or some of DNP63A, GRHL2, TFAP2A, cMYC, LEF1, FOXD1, PRDM1, or SHH.
A gene transduction vector for inducing the neogenesis of skin appendages or enhancing skin appendage function in vivo by transducing a gene encoding all or some of LEF1, FOXD1, PRDM1, or SHH.
A gene transduction vector for inducing the neogenesis of skin appendages or enhancing skin appendage function in vivo by transducing a gene encoding either or both of FOXD1 and PRDM1.
A gene transduction pharmaceutical comprising a gene transduction vector and an effective amount of a steroid for enhancing gene transduction efficiency or gene expression.
A method for enhancing gene transduction efficiency, wherein a steroid is systemically administered to the subject prior to gene transduction.
A method for treating or preventing a skin disease, skin disorder, or skin function impairment in a subject in need thereof, the method comprising administering a gene transduction vector to the subject via ulcer surface application, intradermal injection, or subcutaneous injection, while systemically or locally administering a steroid to the subject prior to, simultaneously with, or shortly after gene transduction.
A method for treating or preventing a muscle disease, muscle disorder, or muscle function impairment in a subject in need thereof, the method comprising administering a gene transduction vector to the subject via intramuscular injection, while systemically or locally administering a steroid to the subject prior to, simultaneously with, or shortly after gene transduction.
A method for treating or preventing a bone and cartilage disease, bone and cartilage disorder, or bone and cartilage function impairment in a subject in need thereof, the method comprising administering a gene transduction vector to the subject via local injection, while systemically or locally administering a steroid to the subject prior to, simultaneously with, or shortly after gene transduction.
A method for producing an upper limb amputation model animal, comprising repositioning the upper limb of a non-human mammal and subsequently amputating the upper limb at the upper arm, forearm, hand, or finger level.
A method for producing an upper limb amputation model animal, comprising repositioning the upper limb of a non-human mammal and subsequently amputating the upper limb at the forearm level.
A pharmaceutical composition for use as a research reagent or therapeutic agent to stimulate the regeneration of missing limbs or the regeneration of missing limb tissues in mammals, comprising:
A research reagent or pharmaceutical composition for use as a therapeutic agent to stimulate cartilage tissue regeneration in mammals, comprising:
A research reagent or pharmaceutical composition for use as a therapeutic agent to stimulate muscle tissue regeneration in mammals, comprising:
A research reagent or pharmaceutical composition for use as a therapeutic agent to stimulate adipose tissue regeneration in mammals, comprising:
Dependencies are inferred from the claim text.