{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T21:06:05Z","timestamp":1781211965391,"version":"3.54.1"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cell.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Trends in Biotechnology"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.tibtech.2026.05.010","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:27:04Z","timestamp":1780432024000},"update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plug-in hybrid baculovirus expression vector for high-yield recombinant adeno-associated virus gene therapy vector production"],"prefix":"10.1016","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8806-752X","authenticated-orcid":false,"given":"Linda A.","family":"de Jong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7563-1785","authenticated-orcid":false,"given":"Jelmer","family":"Willems","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6572-6107","authenticated-orcid":false,"given":"Adriaan H.","family":"de Wilde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4436-7866","authenticated-orcid":false,"given":"Mels","family":"Schrama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara P.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5662-0466","authenticated-orcid":false,"given":"Dirk E.","family":"Martens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6664-4445","authenticated-orcid":false,"given":"Monique M.","family":"van Oers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9301-0408","authenticated-orcid":false,"given":"Gorben P.","family":"Pijlman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tibtech.2026.05.010_bb0005","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.ymthe.2019.12.010","article-title":"AAV vector immunogenicity in humans: a long journey to successful gene transfer","volume":"28","author":"Verdera","year":"2020","journal-title":"Mol. Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0010","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1016\/j.ymthe.2025.04.045","article-title":"Current clinical applications of AAV-mediated gene therapy","volume":"33","author":"Byrne","year":"2025","journal-title":"Mol. Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0015","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1128\/jvi.8.6.860-863.1971","article-title":"Structural proteins of adenovirus-associated virus type 3","volume":"8","author":"Johnson","year":"1971","journal-title":"J. Virol."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0020","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1089\/hum.2015.050","article-title":"OneBac 2.0: Sf9 cell lines for production of AAV5 vectors with enhanced infectivity and minimal encapsidation of foreign DNA","volume":"26","author":"Mietzsch","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0025","article-title":"Application of the Insect Cell-Baculovirus Expression Vector System in adeno-associated viral production","volume":"14","author":"Wang","year":"2024","journal-title":"Appl. Sci."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0030","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1099\/vir.0.067108-0","article-title":"Thirty years of baculovirus-insect cell protein expression: from dark horse to mainstream technology","volume":"96","author":"van Oers","year":"2015","journal-title":"J. Gen. Virol."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0035","doi-asserted-by":"crossref","first-page":"5949","DOI":"10.1016\/j.vaccine.2017.03.048","article-title":"Modern technology: the preferred biosecurity strategy?","volume":"35","author":"Cox","year":"2017","journal-title":"Vaccine"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0040","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.3390\/vaccines11071218","article-title":"Application of baculovirus expression vector system (BEVS) in vaccine development","volume":"11","author":"Hong","year":"2023","journal-title":"Vaccines (Basel)"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0045","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1089\/10430340260355347","article-title":"Insect cells as a factory to produce adeno-associated virus type 2 vectors","volume":"13","author":"Urabe","year":"2002","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0050","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/mt.2008.35","article-title":"Intron splicing-mediated expression of AAV Rep and Cap genes and production of AAV vectors in insect cells","volume":"16","author":"Chen","year":"2008","journal-title":"Mol. Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0055","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1038\/mt.2009.128","article-title":"A simplified baculovirus-AAV expression vector system coupled with one-step affinity purification yields high-titer rAAV stocks from insect cells","volume":"17","author":"Smith","year":"2009","journal-title":"Mol. Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0060","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.3390\/microorganisms9091799","article-title":"Monobac system\u2014a single baculovirus for the production of rAAV","volume":"9","author":"Galibert","year":"2021","journal-title":"Microorganisms"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0065","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.omtm.2018.05.005","article-title":"A recombinant baculovirus efficiently generates recombinant adeno-associated virus vectors in cultured insect cells and larvae","volume":"10","author":"Wu","year":"2018","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0070","doi-asserted-by":"crossref","DOI":"10.1016\/j.omta.2026.201668","article-title":"Productivity and genetic stability of a novel baculovirus vector for multigene expression from independent transgene loci","volume":"34","author":"de Jong","year":"2026","journal-title":"Mol. Ther. Adv."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0075","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1006\/viro.2001.0854","article-title":"Autographa californica baculoviruses with large genomic deletions are rapidly generated in infected insect cells","volume":"283","author":"Pijlman","year":"2001","journal-title":"Virology"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0080","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1099\/vir.0.19438-0","article-title":"Spontaneous excision of BAC vector sequences from bacmid-derived baculovirus expression vectors upon passage in insect cells","volume":"84","author":"Pijlman","year":"2003","journal-title":"J. Gen. Virol."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0085","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1756-6606-7-17","article-title":"Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons","volume":"7","author":"Choi","year":"2014","journal-title":"Mol. Brain"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0090","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41434-021-00296-0","article-title":"Rational engineering of a functional CpG-free ITR for AAV gene therapy","volume":"29","author":"Pan","year":"2022","journal-title":"Gene Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0095","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.3390\/v12121448","article-title":"Relocation of the attTn7 transgene insertion site in bacmid DNA enhances baculovirus genome stability and recombinant protein expression in insect cells","volume":"12","author":"Pijlman","year":"2020","journal-title":"Viruses"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0100","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.ymthe.2019.11.005","article-title":"GPR108 is a highly conserved AAV entry factor","volume":"28","author":"Dudek","year":"2020","journal-title":"Mol. Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0105","doi-asserted-by":"crossref","first-page":"269","DOI":"10.2144\/000114170","article-title":"Comparative next-generation sequencing of adeno-associated virus inverted terminal repeats","volume":"56","author":"Petri","year":"2014","journal-title":"Biotechniques"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0110","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2024.101215","article-title":"Thorough molecular configuration analysis of noncanonical AAV genomes in AAV vector preparations","volume":"32","author":"Zhang","year":"2024","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0115","doi-asserted-by":"crossref","first-page":"3548","DOI":"10.1128\/JVI.02974-13","article-title":"Superinfection exclusion in alphabaculovirus infections is concomitant with actin reorganization","volume":"88","author":"Beperet","year":"2014","journal-title":"J. Virol."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0120","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2025.1679358","article-title":"Impact of multiplicity of infection and baculovirus co-infection ratio on recombinant adeno-associated virus vector production in insect cells","volume":"13","author":"Schrama","year":"2025","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0125","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.omtm.2022.10.015","article-title":"Development of an insect cell-based adeno-associated virus packaging cell line employing advanced Rep gene expression control system","volume":"27","author":"Moreno","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0130","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1089\/hum.2013.184","article-title":"OneBac: platform for scalable and high-titer production of adeno-associated virus serotype 1-12 vectors for gene therapy","volume":"25","author":"Mietzsch","year":"2014","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0135","doi-asserted-by":"crossref","first-page":"9441","DOI":"10.1128\/JVI.74.20.9441-9450.2000","article-title":"Adeno-associated virus type 2 Rep78 induces apoptosis through caspase activation independently of p53","volume":"74","author":"Schmidt","year":"2000","journal-title":"J. Virol."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0140","doi-asserted-by":"crossref","first-page":"13634","DOI":"10.1073\/pnas.0504583102","article-title":"How adeno-associated virus Rep78 protein arrests cells completely in S phase","volume":"102","author":"Berthet","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0145","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1089\/hum.2010.250","article-title":"Reproducible high yields of recombinant adeno-associated virus produced using invertebrate cells in 0.02-to 200-liter cultures","volume":"22","author":"Cecchini","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0150","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1089\/hum.2010.241","article-title":"A versatile adeno-associated virus vector producer cell line method for scalable vector production of different serotypes","volume":"22","author":"Yuan","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0155","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/bit.28562","article-title":"Enhancing the production of recombinant adeno-associated virus in synthetic cell lines through systematic characterization","volume":"121","author":"Lu","year":"2024","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0160","doi-asserted-by":"crossref","first-page":"22657","DOI":"10.1021\/acsomega.4c10900","article-title":"Improving AAV production yield and quality for different serotypes using distinct processing methods","volume":"10","author":"Khaparde","year":"2025","journal-title":"ACS Omega"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0165","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s00449-025-03167-9","article-title":"Improved productivity of recombinant adeno-associated virus (rAAV) via triple transfection of HEK293 cells using perfusion cultivation","volume":"48","author":"Nie","year":"2025","journal-title":"Bioprocess Biosyst. Eng."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0170","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1089\/hum.2009.004","article-title":"Scalable recombinant adeno-associated virus production using recombinant herpes simplex virus type 1 coinfection of suspension-adapted mammalian cells","volume":"20","author":"Thomas","year":"2009","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0175","doi-asserted-by":"crossref","first-page":"e01813","DOI":"10.1128\/mBio.01813-21","article-title":"Two-component nanoparticle vaccine displaying glycosylated spike S1 domain induces neutralizing antibody response against SARS-CoV-2 variants","volume":"12","author":"Van Oosten","year":"2021","journal-title":"mBio"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0180","doi-asserted-by":"crossref","DOI":"10.1038\/mtm.2016.35","article-title":"Rapid, scalable, and low-cost purification of recombinant adeno-associated virus produced by baculovirus expression vector system","volume":"3","author":"Buclez","year":"2016","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0185","article-title":"Improved seamless mutagenesis by recombineering using ccdB for counterselection","volume":"42","author":"Wang","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0190","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/978-1-0716-3961-0_8","article-title":"Scarless baculovirus genome editing using lambda-red recombineering in E. coli","volume":"2829","author":"de Jong","year":"2024","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0195","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0200","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0205","doi-asserted-by":"crossref","first-page":"785","DOI":"10.2144\/000113238","article-title":"A rapid method for titrating baculovirus stocks using the Sf-9 Easy Titer cell line","volume":"47","author":"Hopkins","year":"2009","journal-title":"Biotechniques"},{"key":"10.1016\/j.tibtech.2026.05.010_bb0210","doi-asserted-by":"crossref","first-page":"4566","DOI":"10.1128\/jvi.67.8.4566-4579.1993","article-title":"Efficient generation of infectious recombinant baculoviruses by site-specific transposon-mediated insertion of foreign genes into a baculovirus genome propagated in Escherichia coli","volume":"67","author":"Luckow","year":"1993","journal-title":"J. Virol."},{"key":"10.1016\/j.tibtech.2026.05.010_bb0215","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"Fastp: an ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"}],"container-title":["Trends in Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167779926001952?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167779926001952?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T20:43:29Z","timestamp":1781210609000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167779926001952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":43,"alternative-id":["S0167779926001952"],"URL":"https:\/\/doi.org\/10.1016\/j.tibtech.2026.05.010","relation":{},"ISSN":["0167-7799"],"issn-type":[{"value":"0167-7799","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Plug-in hybrid baculovirus expression vector for high-yield recombinant adeno-associated virus gene therapy vector production","name":"articletitle","label":"Article Title"},{"value":"Trends in Biotechnology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tibtech.2026.05.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}]}}