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We discovered a new type of IAV DIP named \u201cOP7\u201d that carries point mutations in its genome segment (Seg) 7 instead of a deletion as in conventional DIPs (cDIPs). Recently, using genetic engineering tools, we generated \u201cOP7 chimera DIPs\u201d that carry point mutations in Seg\u00a07 plus a deletion in Seg\u00a01. Together with cDIPs, OP7 chimera DIPs were produced in shake flasks in the absence of infectious standard virus (STV), rendering UV inactivation unnecessary. However, only part of the virions harvested were OP7 chimera DIPs (78.7%) and total virus titers were relatively low. Here, we describe the establishment of an OP7 chimera DIP production process applicable for large-scale production. To increase total virus titers, we reduced temperature from 37 to 32\u00a0\u00b0C during virus replication. Production of almost pure OP7 chimera DIP preparations (99.7%) was achieved with a high titer of 3.24\u00a0log<jats:sub>10<\/jats:sub>(HAU\/100\u00a0\u00b5L). This corresponded to an 11-fold increase relative to the initial process. Next, this process was transferred to a stirred tank bioreactor resulting in comparable yields. Moreover, DIP harvests purified and concentrated by steric exclusion chromatography displayed an increased interfering efficacy in vitro. Finally, a perfusion process with perfusion rate control was established, resulting in a 79-fold increase in total virus yields compared to the original batch process in shake flasks. Again, a very high purity of OP7 chimera DIPs was obtained. This process could thus be an excellent starting point for good manufacturing practice production of DIPs for use as antivirals.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Key points<\/jats:title>\n            <jats:p>\u2022 <jats:italic>Scalable cell culture-based process for highly effective antiviral OP7 chimera DIPs<\/jats:italic>\n            <\/jats:p>\n            <jats:p>\u2022 <jats:italic>Production of almost pure OP7 chimera DIPs in the absence of infectious virus<\/jats:italic>\n            <\/jats:p>\n            <jats:p>\u2022 <jats:italic>Perfusion mode production and purification train results in very high titers<\/jats:italic>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00253-023-12959-6","type":"journal-article","created":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T09:02:51Z","timestamp":1705136571000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Production of antiviral \u201cOP7 chimera\u201d defective interfering particles free of infectious virus"],"prefix":"10.1007","volume":"108","author":[{"given":"Lars","family":"Pelz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Dogra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Marichal-Gallardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc Dominique","family":"Hein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada","family":"Hemissi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3943-9718","authenticated-orcid":false,"given":"Sascha Young","family":"Kupke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Genzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Reichl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,13]]},"reference":[{"issue":"3","key":"12959_CR1","doi-asserted-by":"publisher","first-page":"e0212757","DOI":"10.1371\/journal.pone.0212757","volume":"14","author":"N Bdeir","year":"2019","unstructured":"Bdeir N, Arora P, G\u00e4rtner S, Hoffmann M, Reichl U, P\u00f6hlmann S, Winkler M (2019) A system for production of defective interfering particles in the absence of infectious influenza A virus. 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