Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer
Recombinant adeno-associated viruses (AAVs) have emerged as promising gene delivery vehicles resulting in three US Food and Drug Administration (FDA) and one European Medicines Agency (EMA)-approved AAV-based gene therapies. Despite being a leading platform for therapeutic gene transfer in several c...
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| Veröffentlicht in: | BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy biopharmaceuticals, and gene therapy, 2023-05, Vol.37 (3), p.311-329 |
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| container_title | BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy |
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| creator | Arjomandnejad, Motahareh Dasgupta, Ishani Flotte, Terence R. Keeler, Allison M. |
| description | Recombinant adeno-associated viruses (AAVs) have emerged as promising gene delivery vehicles resulting in three US Food and Drug Administration (FDA) and one European Medicines Agency (EMA)-approved AAV-based gene therapies. Despite being a leading platform for therapeutic gene transfer in several clinical trials, host immune responses against the AAV vector and transgene have hampered their widespread application. Multiple factors, including vector design, dose, and route of administration, contribute to the overall immunogenicity of AAVs. The immune responses against the AAV capsid and transgene involve an initial innate sensing. The innate immune response subsequently triggers an adaptive immune response to elicit a robust and specific response against the AAV vector. AAV gene therapy clinical trials and preclinical studies provide important information about the immune-mediated toxicities associated with AAV, yet studies suggest preclinical models fail to precisely predict the outcome of gene delivery in humans. This review discusses the contribution of the innate and adaptive immune response against AAVs, highlighting the challenges and potential strategies to mitigate these responses, thereby enhancing the therapeutic potential of AAV gene therapy. |
| doi_str_mv | 10.1007/s40259-023-00585-7 |
| format | Article |
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Despite being a leading platform for therapeutic gene transfer in several clinical trials, host immune responses against the AAV vector and transgene have hampered their widespread application. Multiple factors, including vector design, dose, and route of administration, contribute to the overall immunogenicity of AAVs. The immune responses against the AAV capsid and transgene involve an initial innate sensing. The innate immune response subsequently triggers an adaptive immune response to elicit a robust and specific response against the AAV vector. AAV gene therapy clinical trials and preclinical studies provide important information about the immune-mediated toxicities associated with AAV, yet studies suggest preclinical models fail to precisely predict the outcome of gene delivery in humans. This review discusses the contribution of the innate and adaptive immune response against AAVs, highlighting the challenges and potential strategies to mitigate these responses, thereby enhancing the therapeutic potential of AAV gene therapy.</description><identifier>ISSN: 1173-8804</identifier><identifier>EISSN: 1179-190X</identifier><identifier>DOI: 10.1007/s40259-023-00585-7</identifier><identifier>PMID: 36862289</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adaptive immunity ; Antibodies ; Antigens ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Clinical trials ; Cytokines ; Cytotoxicity ; Dependovirus - genetics ; Drug dosages ; Expression vectors ; FDA approval ; Gene therapy ; Gene transfer ; Gene Transfer Techniques ; Genetic Therapy - adverse effects ; Genetic Therapy - methods ; Genetic Vectors ; Genomes ; Hemophilia ; Humans ; Immune response ; Immune system ; Immunity, Innate ; Immunogenicity ; Innate immunity ; Liver ; Molecular Medicine ; Pathogens ; Pattern recognition ; Pharmacotherapy ; Proteins ; Review ; Review Article ; Vectors (Biology)</subject><ispartof>BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy, 2023-05, Vol.37 (3), p.311-329</ispartof><rights>The Author(s) 2023</rights><rights>2023. 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Despite being a leading platform for therapeutic gene transfer in several clinical trials, host immune responses against the AAV vector and transgene have hampered their widespread application. Multiple factors, including vector design, dose, and route of administration, contribute to the overall immunogenicity of AAVs. The immune responses against the AAV capsid and transgene involve an initial innate sensing. The innate immune response subsequently triggers an adaptive immune response to elicit a robust and specific response against the AAV vector. AAV gene therapy clinical trials and preclinical studies provide important information about the immune-mediated toxicities associated with AAV, yet studies suggest preclinical models fail to precisely predict the outcome of gene delivery in humans. This review discusses the contribution of the innate and adaptive immune response against AAVs, highlighting the challenges and potential strategies to mitigate these responses, thereby enhancing the therapeutic potential of AAV gene therapy.</description><subject>Adaptive immunity</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Clinical trials</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Dependovirus - genetics</subject><subject>Drug dosages</subject><subject>Expression vectors</subject><subject>FDA approval</subject><subject>Gene therapy</subject><subject>Gene transfer</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - adverse effects</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Genomes</subject><subject>Hemophilia</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity, Innate</subject><subject>Immunogenicity</subject><subject>Innate immunity</subject><subject>Liver</subject><subject>Molecular Medicine</subject><subject>Pathogens</subject><subject>Pattern recognition</subject><subject>Pharmacotherapy</subject><subject>Proteins</subject><subject>Review</subject><subject>Review Article</subject><subject>Vectors (Biology)</subject><issn>1173-8804</issn><issn>1179-190X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU1rFTEUhoNY7If-ARcScFMXqfmaSbIRhqK1UCiU68VdyGROril3kprMFPrvnfa29WPh6gTOc96Tw4PQW0ZPGKXqY5WUN4ZQLgiljW6IeoEOGFOGMEO_v3x4C6I1lfvosNZrSmkrjHqF9kWrW861OUCr83GcU95Aij5OdzgHfAU-j31MLk24GyBl0tWafXQTDHgdy1zxcdetP-A1-CmXikMu-AwS4FVxqQYor9FecNsKbx7rEfr25fPq9Cu5uDw7P-0uiJdKTkQ1fW-0AeqMZkFJNZggvOBDo1gjwiBBgfS89yH0jHEVes-0DHJQxmnBmThCn3a5N3M_wuAhTcVt7U2Joyt3Nrto_-6k-MNu8q01RhkmzRJw_BhQ8s8Z6mTHWD1sty5BnqvlSrOWaaPpgr7_B73Oc0nLeZbrBWlbKdVC8R3lS661QHj-DKP2XprdSbOLNPsgzd4PvfvzjOeRJ0sLIHZAXVppA-X37v_E_gKxaaLA</recordid><startdate>20230501</startdate><enddate>20230501</enddate><creator>Arjomandnejad, Motahareh</creator><creator>Dasgupta, Ishani</creator><creator>Flotte, Terence R.</creator><creator>Keeler, Allison M.</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>4T-</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5202-4616</orcidid></search><sort><creationdate>20230501</creationdate><title>Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer</title><author>Arjomandnejad, Motahareh ; 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| ispartof | BioDrugs : clinical immunotherapeutics, biopharmaceuticals, and gene therapy, 2023-05, Vol.37 (3), p.311-329 |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Adaptive immunity Antibodies Antigens Biomedical and Life Sciences Biomedicine Cancer Research Clinical trials Cytokines Cytotoxicity Dependovirus - genetics Drug dosages Expression vectors FDA approval Gene therapy Gene transfer Gene Transfer Techniques Genetic Therapy - adverse effects Genetic Therapy - methods Genetic Vectors Genomes Hemophilia Humans Immune response Immune system Immunity, Innate Immunogenicity Innate immunity Liver Molecular Medicine Pathogens Pattern recognition Pharmacotherapy Proteins Review Review Article Vectors (Biology) |
| title | Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer |
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