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The most common medium to deliver genetic material to cells is via viral vectors; and with respect to the central nervous system, adeno-associated viral (AAV) vectors are a popular choice. The most successful example of AAV-based gene therapy for neurodegenerative disorders is Zolgensma\u00a9 which is a transformative intravenous therapy given to babies with spinal muscular atrophy. However, the field has stalled in achieving safe drug delivery to the central nervous system in adults for which treatments for disorders such as amyotrophic lateral sclerosis are desperately needed. Surgical gene therapy delivery has been proposed as a potential solution to this problem. While the field of the so-called regenerative neurosurgery has yielded pre-clinical optimism, several challenges have emerged. This review seeks to explore the field of regenerative neurosurgery with respect to AAV-based gene therapy for neurodegenerative diseases, its progress so far and the challenges that need to be overcome.<\/jats:p>","DOI":"10.1007\/s00701-024-06028-8","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T15:05:26Z","timestamp":1710428726000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Taking the knife to neurodegeneration: a review of surgical gene therapy delivery to the CNS"],"prefix":"10.1007","volume":"166","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-3784","authenticated-orcid":false,"given":"Andrea","family":"Perera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Brock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aminul","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyoumars","family":"Ashkan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"issue":"3685","key":"6028_CR1","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1126\/science.149.3685.754","volume":"149","author":"RW Atchinson","year":"1965","unstructured":"Atchinson RW, Casto BC, Hammon WM (1965) Adenovirus-associated defective virus particles. 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