{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T10:10:01Z","timestamp":1784196601828,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Adeno\u2010associated virus (AAV) gene therapy is a transformative treatment for genetic disorders, providing a clinically proven in vivo delivery system capable of vectorizing diverse payloads\u2014including therapeutic proteins, antibodies or fragments, and nucleic acids such as ASOs and siRNAs. Manufacturing AAVs presents distinct challenges, particularly the need for effective cell lysis to recover intracellular AAV particles. Traditional lysis methods, including detergent\u2010based approaches like Triton X\u2010100 and Tween 20 (polysorbate 20), and mechanical approaches such as microfluidization, struggle with scalability, regulatory compliance, and insufficient lysis efficiency. To overcome these challenges, we developed a novel mechanical cell lysis (MCL) method using hollow fiber filters that can be implemented for single use manufacturing. The innovative basis of design had to be commercially feasible for implementation in a single use facility as well as being designed to be environmentally friendly, scalable, and fully compatible with GMP standards. In this publication, we share the development and implementation of MCL showcasing success proof of concept, followed by detailed parameter optimization and rigorous product quality assessment, and finally with the successful at scale\u2010up implementation at 500\u2009L for two cell types proving the ability to use for different production platforms. In conclusion, MCL offers substantial advantages over conventional lysis methods, including enhanced versatility, robustness, environmental sustainability, and simplicity in deployment, positioning it as a superior option for large\u2010scale AAV production.<\/jats:p>","DOI":"10.1002\/bit.70309","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:48:34Z","timestamp":1784195314000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a Novel, Eco\u2010Friendly Mechanical Cell Lysis Process Using Hollow Fiber Filter for AAV Manufacturing"],"prefix":"10.1002","author":[{"given":"Mario","family":"Jabra","sequence":"first","affiliation":[{"name":"Sanofi R&amp;D Global CMC Development, Genomic Medicine Unit CMC Purification Process Development Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Butler","sequence":"additional","affiliation":[{"name":"Sanofi R&amp;D Global CMC Development, Genomic Medicine Unit CMC Purification Process Development Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfen","family":"Ma","sequence":"additional","affiliation":[{"name":"Sanofi R&amp;D Global CMC Development, Genomic Medicine Unit CMC Purification Process Development Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Figueroa","sequence":"additional","affiliation":[{"name":"Sanofi R&amp;D Global CMC Development, Genomic Medicine Unit CMC Purification Process Development Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanli","family":"Song","sequence":"additional","affiliation":[{"name":"Sanofi R&amp;D Global CMC Development, Genomic Medicine Unit CMC Purification Process Development Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"issue":"8","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.tibtech.2009.04.004","article-title":"Advances in Product Release Strategies and Impact on Bioprocess Design","volume":"27","author":"Balasundaram B.","year":"2009","journal-title":"Trends in Biotechnology"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/978-1-4939-8730-6_17","article-title":"Scalable Production and Purification of Adeno\u2010Associated Viral Vectors (AAV)","volume":"1850","author":"Blessing D.","year":"2018","journal-title":"Methods in Molecular Biology"},{"issue":"14","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.186254","article-title":"The Actin Cortex at a Glance","volume":"131","author":"Chugh P.","year":"2018","journal-title":"Journal of Cell Science"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","DOI":"10.1038\/mtm.2015.24","article-title":"Simple Downstream Process Based on Detergent Treatment Improves Yield and In Vivo Transduction Efficacy of Adeno\u2010Associated Virus Vectors","volume":"2","author":"Dias Florencio G.","year":"2015","journal-title":"Molecular Therapy \u2010 Methods & Clinical Development"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.seppur.2013.03.017","article-title":"Recent Progresses in Polymeric Hollow Fiber Membrane Preparation, Characterization and Applications","volume":"111","author":"Feng C. 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