{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:23:37Z","timestamp":1789129417905,"version":"build-2803163510"},"reference-count":24,"publisher":"SAGE Publications","issue":"19-20","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>\n                    The Platform Vector-Gene Therapy (PaVe-GT) program is a National Institutes of Health (NIH) initiative that aims to develop adeno-associated virus (AAV) gene therapies for four monogenic rare diseases, two organic acidemias and two congenital myasthenic syndromes. PaVe-GT\u2019s platform-based approach identifies and diminishes redundancies and applies efficiencies in preclinical, clinical, and regulatory activities. The program\u2019s hypothesis is that implementing these efficiencies can accelerate clinical trial initiation. Based on its platform-centric experience and public-serving mission, the PaVe-GT program actively shares its scientific and regulatory learnings with the public to benefit the development of similar gene therapy products for rare diseases. PaVe-GT\u2019s first investigational AAV gene therapy candidate is AAV serotype 9 human propionyl-CoA carboxylase alpha subunit (AAV9-hPCCA) for propionic acidemia caused by PCCA deficiency, which received initial feedback from the Food and Drug Administration (FDA) in an\n                    <jats:bold>IN<\/jats:bold>\n                    itial\n                    <jats:bold>T<\/jats:bold>\n                    argeted\n                    <jats:bold>E<\/jats:bold>\n                    ngagement for\n                    <jats:bold>R<\/jats:bold>\n                    egulatory\n                    <jats:bold>A<\/jats:bold>\n                    dvice on\n                    <jats:bold>C<\/jats:bold>\n                    BER\/Center for Drug Evaluation and Research (CDER) Produc\n                    <jats:bold>T<\/jats:bold>\n                    s (INTERACT) meeting. Upon further product development that took into consideration the FDA\u2019s initial advice, the program obtained the Agency\u2019s feedback in pre-investigational new drug (IND) (Type B) and Type C meetings. Here, we share our experience from these meetings, including strategy, preparation, pre- and post-meeting feedback from the FDA, and lessons learned during the AAV9-hPCCA regulatory process, which the program plans to apply across the PaVe-GT platform. Topics discussed in the regulatory meetings included animal model and efficacy studies, toxicology study plans, manufacturing of the investigational AAV product, and clinical trial design. The main lessons learned from the pre-IND and Type C meetings for AAV9-hPCCA are: (1) Pharmacology\/Toxicology studies in a single rodent species are sufficient for filing an initial IND; (2) FDA feedback guides product quality improvements and early development of a quantitative potency assay; (3) use of biomarkers as potential surrogate endpoints in a future efficacy trial benefits from collection of data in the natural history study and the first-in-human Phase 1\/2 study; and (4) evidence from the Phase 1\/2 clinical trial could be leveraged to support a license application. Lightly redacted regulatory documents and comprehensive templates developed by the PaVe-GT team are available on the PaVe-GT website.\n                  <\/jats:p>","DOI":"10.1177\/10430342261452217","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T03:51:43Z","timestamp":1781927503000},"page":"932-947","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Adeno-Associated Virus Gene Therapy Translation: Lessons from Early Regulatory Meetings"],"prefix":"10.1177","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6060-2076","authenticated-orcid":false,"given":"Rodica","family":"Stan","sequence":"first","affiliation":[{"name":"Therapeutic Development Branch, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa Madan","family":"Lomash","sequence":"additional","affiliation":[{"name":"Therapeutic Development Branch, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg A.","family":"Shchelochkov","sequence":"additional","affiliation":[{"name":"Organic Acid Research Section, Metabolic Medicine Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irini","family":"Manoli","sequence":"additional","affiliation":[{"name":"Organic Acid Research Section, Metabolic Medicine Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina I.","family":"Galarreta Aima","sequence":"additional","affiliation":[{"name":"Organic Acid Research Section, Metabolic Medicine Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkata","family":"Mangalampalli","sequence":"additional","affiliation":[{"name":"Therapeutic Development Branch, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Organic Acid Research Section, Metabolic Medicine Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy J.","family":"Chandler","sequence":"additional","affiliation":[{"name":"Organic Acid Research Section, Metabolic Medicine Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Li","sequence":"additional","affiliation":[{"name":"Organic Acid Research Section, Metabolic Medicine Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Sloan","sequence":"additional","affiliation":[{"name":"Organic Acid Research Section, Metabolic Medicine Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramod","family":"Terse","sequence":"additional","affiliation":[{"name":"Therapeutic Development Branch, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xu","sequence":"additional","affiliation":[{"name":"Therapeutic Development Branch, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"PaVe-GT Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Dehdashti","sequence":"additional","affiliation":[{"name":"Division of Rare Diseases Research and Innovation, NCATS, NIH, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Division of Rare Diseases Research and Innovation, NCATS, NIH, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten G.","family":"B\u00f6nnemann","sequence":"additional","affiliation":[{"name":"Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles P.","family":"Venditti","sequence":"additional","affiliation":[{"name":"Organic Acid Research Section, Metabolic Medicine Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Ottinger","sequence":"additional","affiliation":[{"name":"Therapeutic Development Branch, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"e_1_3_4_2_1","volume-title":"Highlights of Prescribing Information \u2013 LUXTURNA","author":"Spark Therapeutics, Inc","year":"2022","unstructured":"1.Spark Therapeutics, Inc. 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