{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:15:37Z","timestamp":1788174937599,"version":"build-2803163510"},"reference-count":60,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The separation of empty and full adeno\u2010associated viruses (AAVs) is particularly critical because of the similarity between the two. Anion\u2010exchange chromatography represents a scalable tool, leveraging their slight difference in isoelectric point. However, traditional resin chromatography can only deliver poor resolution, mainly due to the restricted accessibility of the capisds to the bead pores. To cover this gap, in this work, we designed and optimized the separation of empty and full AAVs using anion\u2010exchange membrane chromatography. The role played by flowrate, gradient slope and wash step parameters on the chromatographic resolution was first investigated with two consecutive designs of experiments (DoE). The response surfaces indicated that high process flowrates, that is 15 membrane volumes (MVs)\/min, with a gradient from 115\u00a0mM to 250\u00a0mM sodium acetate in 350 MVs maximize the chromatographic resolution. Then, preparative experiments showed that fast loading is possible, with residence time as short as 24 s, without product breakthrough. Moreover, membrane loading up to 1.2E17 viral particles (vp)\/L\n                    <jats:sub>membrane<\/jats:sub>\n                    could be reached, providing one order of magnitude higher productivity with respect to standard column operations. With these results, we demonstrated the great potential of anion\u2010exchange membrane chromatography in the polishing of AAVs, overcoming traditional limitations of packed\u2010bed operations.\n                  <\/jats:p>","DOI":"10.1002\/biot.70295","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:22:39Z","timestamp":1786954959000},"source":"Crossref","is-referenced-by-count":0,"title":["Anion\u2010Exchange Membrane Chromatography for the Separation of Empty and Full Adeno\u2010Associated Viral Capsids"],"prefix":"10.1002","volume":"21","author":[{"given":"Luca","family":"Ossi","sequence":"first","affiliation":[{"name":"Department of Chemistry Materials and Chemical Engineering Politecnico Di Milano  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuele","family":"Delfino","sequence":"additional","affiliation":[{"name":"Department of Chemistry Materials and Chemical Engineering Politecnico Di Milano  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Marie","sequence":"additional","affiliation":[{"name":"Merck Life Science KGaA  Darmstad Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schulte","sequence":"additional","affiliation":[{"name":"Merck Life Science KGaA  Darmstad Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8130-6495","authenticated-orcid":false,"given":"Mattia","family":"Sponchioni","sequence":"additional","affiliation":[{"name":"Department of Chemistry Materials and Chemical Engineering Politecnico Di Milano  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.175.4025.949"},{"key":"e_1_2_10_3_1","first-page":"151","article-title":"State\u2010of\u2010the\u2010Art Human Gene Therapy: Part II. 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