{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:17:15Z","timestamp":1792120635277,"version":"4.4.0"},"reference-count":179,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"STI 2030-Major Project","award":["2021ZD0201703"],"award-info":[{"award-number":["2021ZD0201703"]}]},{"name":"STI 2030-Major Project","award":["32170957"],"award-info":[{"award-number":["32170957"]}]},{"name":"STI 2030-Major Project","award":["31970913"],"award-info":[{"award-number":["31970913"]}]},{"name":"STI 2030-Major Project","award":["2021A1515012156"],"award-info":[{"award-number":["2021A1515012156"]}]},{"name":"STI 2030-Major Project","award":["2019B030335001"],"award-info":[{"award-number":["2019B030335001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021ZD0201703"],"award-info":[{"award-number":["2021ZD0201703"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170957"],"award-info":[{"award-number":["32170957"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970913"],"award-info":[{"award-number":["31970913"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021A1515012156"],"award-info":[{"award-number":["2021A1515012156"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019B030335001"],"award-info":[{"award-number":["2019B030335001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2021ZD0201703"],"award-info":[{"award-number":["2021ZD0201703"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["32170957"],"award-info":[{"award-number":["32170957"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["31970913"],"award-info":[{"award-number":["31970913"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2021A1515012156"],"award-info":[{"award-number":["2021A1515012156"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2019B030335001"],"award-info":[{"award-number":["2019B030335001"]}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["2021ZD0201703"],"award-info":[{"award-number":["2021ZD0201703"]}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["32170957"],"award-info":[{"award-number":["32170957"]}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["31970913"],"award-info":[{"award-number":["31970913"]}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["2021A1515012156"],"award-info":[{"award-number":["2021A1515012156"]}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["2019B030335001"],"award-info":[{"award-number":["2019B030335001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As the blood\u2013brain barrier (BBB) prevents molecules from accessing the central nervous system (CNS), the traditional systemic delivery of chemical drugs limits the development of neurological drugs. However, in recent years, innovative therapeutic strategies have tried to bypass the restriction of traditional drug delivery methods. In vivo gene therapy refers to emerging biopharma vectors that carry the specific genes and target and infect specific tissues; these infected cells and tissues then undergo fundamental changes at the genetic level and produce therapeutic proteins or substances, thus providing therapeutic benefits. Clinical and preclinical trials mainly utilize adeno-associated viruses (AAVs), lentiviruses (LVs), and other viruses as gene vectors for disease investigation. Although LVs have a higher gene-carrying capacity, the vector of choice for many neurological diseases is the AAV vector due to its safety and long-term transgene expression in neurons. Here, we review the basic biology of AAVs and summarize some key issues in recombinant AAV (rAAV) engineering in gene therapy research; then, we summarize recent clinical trials using rAAV treatment for neurological diseases and provide translational perspectives and future challenges on target selection.<\/jats:p>","DOI":"10.3390\/ijms26052213","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T10:46:46Z","timestamp":1740739606000},"page":"2213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Progress in AAV-Mediated In Vivo Gene Therapy and Its Applications in Central Nervous System Diseases"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9467-6777","authenticated-orcid":false,"given":"Shuming","family":"Wang","sequence":"first","affiliation":[{"name":"Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of Mental Health and Cognitive Science, Center for Studies of Psychological Application, South China Normal University, Guangzhou 510631, China"},{"name":"Key Laboratory of Brain, Cognition and Education Sciences of Ministry of Education, South China Normal University, Guangzhou 510631, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4283-1796","authenticated-orcid":false,"given":"Lin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of Mental Health and Cognitive Science, Center for Studies of Psychological Application, South China Normal University, Guangzhou 510631, China"},{"name":"Key Laboratory of Brain, Cognition and Education Sciences of Ministry of Education, South China Normal University, Guangzhou 510631, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.molimm.2018.06.267","article-title":"Blood-brain barrier (BBB) and the complement landscape","volume":"102","author":"Alexander","year":"2018","journal-title":"Mol. 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