{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T19:30:42Z","timestamp":1772652642777,"version":"3.50.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100011104","name":"Universitat Aut\u00f2noma de Barcelona","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011104","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Appl Microbiol Biotechnol"],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Several strategies have been developed in recent years to improve virus-like particle (VLP)-based vaccine production processes. Among these, the metabolic engineering of cell lines has been one of the most promising approaches. Based on previous work and a proteomic analysis of HEK293 cells producing Human Immunodeficiency Virus-1 (HIV-1) Gag VLPs under transient transfection, four proteins susceptible of enhancing VLP production were identified: ataxia telangiectasia mutated (ATM), ataxia telangiectasia and rad3-related (ATR), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta (PDE\u03b4). The knockdown of ATM, ATR, and PDE\u03b4 in HEK293 cells increased HIV-1 VLP titers in the supernatant by 3.4-, 2.1-, and 2.2-fold, respectively. Also, possible metabolic synergies between plasmids were investigated by statistical design of experiments (DoE), enabling us to identify the optimal production strategy, that was further demonstrated at lab-scale stirred tank bioreactor operated in perfusion, significantly increasing both VLPs specific and volumetric productivities to 8.3\u2009\u00d7\u200910\n                      <jats:sup>3<\/jats:sup>\n                      VLPs\/cellxday and 7.5\u2009\u00d7\u200910\n                      <jats:sup>12<\/jats:sup>\n                      VLPs\/Lxday, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:italic>\u2022 ATM, ATR, and PDE\u03b4 knockdowns increased VLP production in HEK293 cells.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:italic>\u2022 Knockdown of ATM increased budding efficiency and extracellular vesicle concentration.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:italic>\u2022 ATM knockdown could be intensified to bioreactor scale operated in perfusion.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00253-024-13389-8","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T19:30:52Z","timestamp":1735846252000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted knockdown of ATM, ATR, and PDE\u03b4 increases Gag HIV-1 VLP production in HEK293 cells"],"prefix":"10.1007","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5259-8070","authenticated-orcid":false,"given":"Andy","family":"D\u00edaz-Maneh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9892-6762","authenticated-orcid":false,"given":"Pol","family":"P\u00e9rez-Rubio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina Rigau","family":"Granes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laia","family":"Bosch-Molist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9993-6332","authenticated-orcid":false,"given":"Jes\u00fas","family":"Lavado-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4060-9887","authenticated-orcid":false,"given":"Francesc","family":"G\u00f2dia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3639-2793","authenticated-orcid":false,"given":"Laura","family":"Cervera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"13389_CR1","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1134\/S0026893319030026","volume":"53","author":"A Anisenko","year":"2019","unstructured":"Anisenko A, Gottikh M (2019) Role of cellular DNA repair systems in HIV-1 replication. Mol Biol 53:313\u2013322. https:\/\/doi.org\/10.1134\/S0026893319030026","journal-title":"Mol Biol"},{"key":"13389_CR2","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1016\/j.biotechadv.2018.04.011","volume":"36","author":"JM Bielser","year":"2018","unstructured":"Bielser JM, Wolf M, Souquet J, Broly H, Morbidelli M (2018) Perfusion mammalian cell culture for recombinant protein manufacturing \u2013 A critical review. Biotechnol Adv 36:1328\u20131340. https:\/\/doi.org\/10.1016\/j.biotechadv.2018.04.011","journal-title":"Biotechnol Adv"},{"key":"13389_CR3","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1093\/nar\/gkh508","volume":"32","author":"WD Block","year":"2004","unstructured":"Block WD, Merkle D, Meek K, Lees-Miller SP (2004) Selective inhibition of the DNA-dependent protein kinase (DNA-PK) by the radiosensitizing agent caffeine. Nucleic Acids Res 32:1967\u20131972. https:\/\/doi.org\/10.1093\/nar\/gkh508","journal-title":"Nucleic Acids Res"},{"key":"13389_CR4","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.bej.2016.07.003","volume":"114","author":"MM Buffo","year":"2016","unstructured":"Buffo MM, Corr\u00eaa LJ, Esperan\u00e7a MN, Cruz AJG, Farinas CS, Badino AC (2016) Influence of dual-impeller type and configuration on oxygen transfer, power consumption, and shear rate in a stirred tank bioreactor. Biochem Eng J 114:130\u2013139. https:\/\/doi.org\/10.1016\/j.bej.2016.07.003","journal-title":"Biochem Eng J"},{"key":"13389_CR5","doi-asserted-by":"publisher","first-page":"e1002347","DOI":"10.1371\/journal.ppat.1002347","volume":"7","author":"M Caillet","year":"2011","unstructured":"Caillet M, Janvier K, Pelchen-Matthews A, Delcroix-Gen\u00eate D, Camus G, Marsh M, Berlioz-Torrent C (2011) Rab7A is required for efficient production of infectious HIV-1. PLoS Pathog 7:e1002347. https:\/\/doi.org\/10.1371\/journal.ppat.1002347","journal-title":"PLoS Pathog"},{"key":"13389_CR6","doi-asserted-by":"publisher","first-page":"9935","DOI":"10.1007\/s00253-015-6842-4","volume":"99","author":"L Cervera","year":"2015","unstructured":"Cervera L, Fuenmayor J, Gonz\u00e1lez-Dom\u00ednguez I, Guti\u00e9rrez-Granados S, Segura MM, G\u00f2dia F (2015a) Selection and optimization of transfection enhancer additives for increased virus-like particle production in HEK293 suspension cell cultures. Appl Microbiol Biotechnol 99:9935\u20139949. https:\/\/doi.org\/10.1007\/s00253-015-6842-4","journal-title":"Appl Microbiol Biotechnol"},{"key":"13389_CR7","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1002\/bit.25503","volume":"112","author":"L Cervera","year":"2015","unstructured":"Cervera L, Guti\u00e9rrez-Granados S, Berrow NS, Segura MM, G\u00f2dia F (2015b) Extended gene expression by medium exchange and repeated transient transfection for recombinant protein production enhancement. Biotechnol Bioeng 112:934\u2013946. https:\/\/doi.org\/10.1002\/bit.25503","journal-title":"Biotechnol Bioeng"},{"key":"13389_CR8","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.1002\/bit.26367","volume":"114","author":"L Cervera","year":"2017","unstructured":"Cervera L, Gonz\u00e1lez-Dom\u00ednguez I, Segura MM, G\u00f2dia F (2017) Intracellular characterization of Gag VLP production by transient transfection of HEK 293 cells. Biotechnol Bioeng 114:2507\u20132517. https:\/\/doi.org\/10.1002\/bit.26367","journal-title":"Biotechnol Bioeng"},{"key":"13389_CR9","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/0024-3205(88)90517-6","volume":"43","author":"OH Choi","year":"1988","unstructured":"Choi OH, Shamim MT, Padgett WL, Daly JW (1988) Caffeine and theophylline analogues: Correlation of behavioral effects with activity as adenosine receptor antagonists and as phosphodiesterase inhibitors. Life Sci 43:387\u2013398. https:\/\/doi.org\/10.1016\/0024-3205(88)90517-6","journal-title":"Life Sci"},{"key":"13389_CR10","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.inmuno.2012.08.002","volume":"2","author":"E Crisci","year":"2012","unstructured":"Crisci E, B\u00e1rcena J, Montoya M (2012) Virus-like particle-based vaccines for animal viral infections. Inmunolog\u00eda 2:102\u2013116. https:\/\/doi.org\/10.1016\/j.inmuno.2012.08.002","journal-title":"Inmunolog\u00eda"},{"key":"13389_CR11","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1128\/jvi.79.4.2058-2065.2005","volume":"79","author":"R Daniel","year":"2005","unstructured":"Daniel R, Marusich E, Argyris E, Zhao RY, Skalka AM, Pomerantz RJ (2005) Caffeine inhibits human immunodeficiency virus type 1 transduction of nondividing cells. J Virol 79:2058\u20132065. https:\/\/doi.org\/10.1128\/jvi.79.4.2058-2065.2005","journal-title":"J Virol"},{"key":"13389_CR12","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1007\/s00705-020-04531-8","volume":"165","author":"F Docando","year":"2020","unstructured":"Docando F, Casado C, Pernas M, Mota-Biosca A, L\u00f3pez-Gal\u00edndez C, Olivares I (2020) Characterizing the antiviral effect of an ATR inhibitor on human immunodeficiency virus type 1 replication. Arch Virol 165:683\u2013690. https:\/\/doi.org\/10.1007\/s00705-020-04531-8","journal-title":"Arch Virol"},{"key":"13389_CR13","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1089\/hum.2010.068","volume":"22","author":"BL Ellis","year":"2011","unstructured":"Ellis BL, Potts PR, Porteus MH (2011) Creating higher titer lentivirus with caffeine. Hum Gene Ther 22:93\u2013100. https:\/\/doi.org\/10.1089\/hum.2010.068","journal-title":"Hum Gene Ther"},{"key":"13389_CR14","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.nbt.2017.07.010","volume":"39","author":"J Fuenmayor","year":"2017","unstructured":"Fuenmayor J, G\u00f2dia F, Cervera L (2017) Production of virus-like particles for vaccines. N Biotechnol 39:174\u2013180. https:\/\/doi.org\/10.1016\/j.nbt.2017.07.010","journal-title":"N Biotechnol"},{"key":"13389_CR15","doi-asserted-by":"publisher","first-page":"4477","DOI":"10.1007\/s00253-018-8930-8","volume":"102","author":"J Fuenmayor","year":"2018","unstructured":"Fuenmayor J, Cervera L, Rigau C, G\u00f2dia F (2018) Enhancement of HIV-1 VLP production using gene inhibition strategies. Appl Microbiol Biotechnol 102:4477\u20134487. https:\/\/doi.org\/10.1007\/s00253-018-8930-8","journal-title":"Appl Microbiol Biotechnol"},{"key":"13389_CR16","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1083\/jcb.201409082","volume":"209","author":"PP Gerber","year":"2015","unstructured":"Gerber PP, Cabrini M, Jancic C, Paoletti L, Banchio C, von Bilderling C, Sigaut L, Pietrasanta LI, Duette G, Freed EO, de Saint BG, Moita CF, Moita LF, Amigorena S, Benaroch P, Geffner J, Ostrowski M (2015) Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate. J Cell Biol 209:435\u2013452. https:\/\/doi.org\/10.1083\/jcb.201409082","journal-title":"J Cell Biol"},{"key":"13389_CR17","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/nmeth.1318","volume":"6","author":"DG Gibson","year":"2009","unstructured":"Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA, Smith HO (2009) Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods 6:343\u2013345. https:\/\/doi.org\/10.1038\/nmeth.1318","journal-title":"Nat Methods"},{"key":"13389_CR18","unstructured":"Godia-Casablancas F, Bosch-Tubert M-F, Garcia-Martinez M, Cervera-Gracia L, Leon-Madrenas X, Molas-Laplana M, Gutierrez-Granados S (2022) Methods for the manufacture of recombinant viral vectors"},{"key":"13389_CR19","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.nbt.2018.09.005","volume":"49","author":"I Gonz\u00e1lez-Dom\u00ednguez","year":"2019","unstructured":"Gonz\u00e1lez-Dom\u00ednguez I, Grimaldi N, Cervera L, Ventosa N, G\u00f2dia F (2019) Impact of physicochemical properties of DNA\/PEI complexes on transient transfection of mammalian cells. N Biotechnol 49:88\u201397. https:\/\/doi.org\/10.1016\/j.nbt.2018.09.005","journal-title":"N Biotechnol"},{"key":"13389_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/v12020223","volume":"12","author":"I Gonz\u00e1lez-Dom\u00ednguez","year":"2020","unstructured":"Gonz\u00e1lez-Dom\u00ednguez I, Puente-Massaguer E, Cervera L, G\u00f2dia F (2020) Quality assessment of virus-like particles at single particle level: A comparative study. Viruses 12:1\u201324. https:\/\/doi.org\/10.3390\/v12020223","journal-title":"Viruses"},{"key":"13389_CR21","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.3390\/vaccines9101154","volume":"9","author":"I Gonz\u00e1lez-Dom\u00ednguez","year":"2021","unstructured":"Gonz\u00e1lez-Dom\u00ednguez I, Lorenzo E, Bernier A, Cervera L, G\u00f2dia F, Kamen A (2021) A four-step purification process for Gag VLPs: from culture supernatant to high-purity lyophilized particles. Vaccines 9:1154. https:\/\/doi.org\/10.3390\/vaccines9101154","journal-title":"Vaccines"},{"key":"13389_CR22","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.jviromet.2013.05.010","volume":"193","author":"S Guti\u00e9rrez-Granados","year":"2013","unstructured":"Guti\u00e9rrez-Granados S, Cervera L, G\u00f2dia F, Carrillo J, Segura MM (2013) Development and validation of a quantitation assay for fluorescently tagged HIV-1 virus-like particles. J Virol Methods 193:85\u201395. https:\/\/doi.org\/10.1016\/j.jviromet.2013.05.010","journal-title":"J Virol Methods"},{"key":"13389_CR23","doi-asserted-by":"publisher","first-page":"8670","DOI":"10.1128\/jvi.74.18.8670-8679.2000","volume":"74","author":"L Hermida-Matsumoto","year":"2000","unstructured":"Hermida-Matsumoto L, Resh MD (2000) Localization of human immunodeficiency virus type 1 Gag and Env at the plasma membrane by confocal imaging. J Virol 74:8670\u20138679. https:\/\/doi.org\/10.1128\/jvi.74.18.8670-8679.2000","journal-title":"J Virol"},{"issue":"1","key":"13389_CR24","doi-asserted-by":"publisher","first-page":"e202007026","DOI":"10.1083\/jcb.202007026","volume":"222","author":"Z Huang","year":"2023","unstructured":"Huang Z, Chen CW, Buj R, Tangudu NK, Fang RS, Leon KE, Dahl ES, Varner EL, von Krusenstiern E, Cole AR, Snyder NW, Aird KM (2023) ATM inhibition drives metabolic adaptation via induction of macropinocytosis. J Cell Biol 222(1):e202007026. https:\/\/doi.org\/10.1083\/jcb.202007026","journal-title":"J Cell Biol"},{"key":"13389_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12896-015-0131-2","volume":"15","author":"TB Jacobs","year":"2015","unstructured":"Jacobs TB, LaFayette PR, Schmitz RJ, Parrott WA (2015) Targeted genome modifications in soybean with CRISPR\/Cas9. BMC Biotechnol 15:1\u201310. https:\/\/doi.org\/10.1186\/s12896-015-0131-2","journal-title":"BMC Biotechnol"},{"key":"13389_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fbioe.2020.00617","volume":"8","author":"J Lavado-Garc\u00eda","year":"2020","unstructured":"Lavado-Garc\u00eda J, Cervera L, G\u00f2dia F (2020a) An alternative perfusion approach for the intensification of virus-like particle production in HEK293 cultures. Front Bioeng Biotechnol 8:1\u201316. https:\/\/doi.org\/10.3389\/fbioe.2020.00617","journal-title":"Front Bioeng Biotechnol"},{"key":"13389_CR27","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1021\/acs.jproteome.9b00601","volume":"19","author":"J Lavado-Garc\u00eda","year":"2020","unstructured":"Lavado-Garc\u00eda J, Jorge I, Cervera L, V\u00e1zquez J, G\u00f2dia F (2020b) Multiplexed quantitative proteomic analysis of HEK293 provides insights into molecular changes associated with the cell density effect, transient transfection, and virus-like particle production. J Proteome Res 19:1085\u20131099. https:\/\/doi.org\/10.1021\/acs.jproteome.9b00601","journal-title":"J Proteome Res"},{"key":"13389_CR28","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1002\/bit.27679","volume":"118","author":"J Lavado-Garc\u00eda","year":"2021","unstructured":"Lavado-Garc\u00eda J, D\u00edaz-Maneh A, Canal-Paul\u00ed N, P\u00e9rez-Rubio P, G\u00f2dia F, Cervera L (2021b) Metabolic engineering of HEK293 cells to improve transient transfection and cell budding of HIV-1 virus-like particles. Biotechnol Bioeng 118:1649\u20131663. https:\/\/doi.org\/10.1002\/bit.27679","journal-title":"Biotechnol Bioeng"},{"key":"13389_CR29","doi-asserted-by":"publisher","first-page":"2660","DOI":"10.1002\/bit.27786","volume":"118","author":"J Lavado-Garc\u00eda","year":"2021","unstructured":"Lavado-Garc\u00eda J, Jorge I, Boix-Besora A, V\u00e1zquez J, G\u00f2dia F, Cervera L (2021c) Characterization of HIV-1 virus-like particles and determination of Gag stoichiometry for different production platforms. Biotechnol Bioeng 118:2660\u20132675. https:\/\/doi.org\/10.1002\/bit.27786","journal-title":"Biotechnol Bioeng"},{"key":"13389_CR30","doi-asserted-by":"publisher","first-page":"4516","DOI":"10.1021\/acs.jproteome.0c00581","volume":"19","author":"J Lavado-Garc\u00eda","year":"2020","unstructured":"Lavado-Garci\u00e1 J, Gonz\u00e1lez-Dom\u00ednguez I, Cervera L, Jorge I, V\u00e1zquez J, G\u00f2dia F (2020c) Molecular characterization of the coproduced extracellular vesicles in HEK293 during virus-like particle production. J Proteome Res 19:4516\u20134532. https:\/\/doi.org\/10.1021\/acs.jproteome.0c00581","journal-title":"J Proteome Res"},{"key":"13389_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0080769","volume":"8","author":"H Ma","year":"2013","unstructured":"Ma H, Zhao XL, Wang XY, Xie XW, Han JC, Guan WL, Wang Q, Zhu L, Ben PX, Wei L (2013) 2\u2019,3\u2019-Cyclic nucleotide 3\u2019-phosphodiesterases inhibit hepatitis B virus replication. PLoS ONE 8:1\u201311. https:\/\/doi.org\/10.1371\/journal.pone.0080769","journal-title":"PLoS ONE"},{"key":"13389_CR32","doi-asserted-by":"publisher","first-page":"e161","DOI":"10.1038\/mtna.2014.12","volume":"3","author":"H Ma","year":"2014","unstructured":"Ma H, Wu Y, Dang Y, Choi JG, Zhang J, Wu H (2014) Pol III promoters to express small RNAs: Delineation of transcription initiation. Mol Ther Nucleic Acids 3:e161. https:\/\/doi.org\/10.1038\/mtna.2014.12","journal-title":"Mol Ther Nucleic Acids"},{"key":"13389_CR33","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1002\/bit.21467","volume":"98","author":"M Mercedes Segura","year":"2007","unstructured":"Mercedes Segura M, Garnier A, Durocher Y, Coelho H, Kamen A (2007) Production of lentiviral vectors by large-scale transient transfection of suspension cultures and affinity chromatography purification. Biotechnol Bioeng 98:789\u2013799. https:\/\/doi.org\/10.1002\/bit.21467","journal-title":"Biotechnol Bioeng"},{"key":"13389_CR34","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.virol.2005.02.015","volume":"335","author":"G Nunnari","year":"2005","unstructured":"Nunnari G, Argyris E, Fang J, Mehlman KE, Pomerantz RJ, Daniel R (2005) Inhibition of HIV-1 replication by caffeine and caffeine-related methylxanthines. Virology 335:177\u2013184. https:\/\/doi.org\/10.1016\/j.virol.2005.02.015","journal-title":"Virology"},{"key":"13389_CR35","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.cell.2009.08.039","volume":"139","author":"D Perez-Caballero","year":"2009","unstructured":"Perez-Caballero D, Zang T, Ebrahimi A, McNatt MW, Gregory DA, Johnson MC, Bieniasz PD (2009) Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell 139:499\u2013511. https:\/\/doi.org\/10.1016\/j.cell.2009.08.039","journal-title":"Cell"},{"key":"13389_CR36","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1586\/erv.10.115","volume":"9","author":"A Rold\u00e3o","year":"2010","unstructured":"Rold\u00e3o A, Mellado MCM, Castilho LR, Carrondo MJT, Alves PM (2010) Virus-like particles in vaccine development. Expert Rev Vaccines 9:1149\u20131176. https:\/\/doi.org\/10.1586\/erv.10.115","journal-title":"Expert Rev Vaccines"},{"key":"13389_CR37","doi-asserted-by":"publisher","first-page":"25879","DOI":"10.1074\/jbc.M303948200","volume":"278","author":"M Roshal","year":"2003","unstructured":"Roshal M, Kim B, Zhu Y, Nghiem P, Planelles V (2003) Activation of the ATR-mediated DNA damage response by the HIV-1 viral protein R. J Biol Chem 278:25879\u201325886. https:\/\/doi.org\/10.1074\/jbc.M303948200","journal-title":"J Biol Chem"},{"key":"13389_CR38","first-page":"4375","volume":"59","author":"JN Sarkaria","year":"1999","unstructured":"Sarkaria JN, Busby EC, Tibbetts RS, Roos P, Taya Y, Karnitz LM, Abraham RT (1999) Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res 59:4375\u20134382","journal-title":"Cancer Res"},{"key":"13389_CR39","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671\u2013675. https:\/\/doi.org\/10.1038\/nmeth.2089","journal-title":"Nat Methods"},{"key":"13389_CR40","doi-asserted-by":"publisher","first-page":"796991","DOI":"10.3389\/fbioe.2021.796991","volume":"9","author":"E Tan","year":"2021","unstructured":"Tan E, Chin CSH, Lim ZFS, Ng SK (2021) HEK293 cell line as a platform to produce recombinant proteins and viral vectors. Front Bioeng Biotechnol 9:796991. https:\/\/doi.org\/10.3389\/fbioe.2021.796991","journal-title":"Front Bioeng Biotechnol"},{"key":"13389_CR41","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1111\/jth.12602","volume":"12","author":"E van der Pol","year":"2014","unstructured":"van der Pol E, Coumans FAW, Grootemaat AE, Gardiner C, Sargent IL, Harrison P, Sturk A, van Leeuwen TG, Nieuwland R (2014) Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J Thromb Haemost 12:1182\u20131192. https:\/\/doi.org\/10.1111\/jth.12602","journal-title":"J Thromb Haemost"},{"key":"13389_CR42","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.chom.2012.08.012","volume":"12","author":"SJ Wilson","year":"2012","unstructured":"Wilson SJ, Schoggins JW, Zang T, Kutluay SB, Jouvenet N, Alim MA, Bitzegeio J, Rice CM, Bieniasz PD (2012) Inhibition of HIV-1 particle assembly by 2\u2032,3\u2032-cyclic- nucleotide 3\u2032-phosphodiesterase. Cell Host Microbe 12:585\u2013597. https:\/\/doi.org\/10.1016\/j.chom.2012.08.012","journal-title":"Cell Host Microbe"},{"key":"13389_CR43","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.virol.2009.10.032","volume":"396","author":"YX Yang","year":"2010","unstructured":"Yang YX, Guen V, Richard J, Cohen EA, Berthoux L (2010) Cell context-dependent involvement of ATR in early stages of retroviral replication. Virology 396:272\u2013279. https:\/\/doi.org\/10.1016\/j.virol.2009.10.032","journal-title":"Virology"},{"key":"13389_CR44","doi-asserted-by":"publisher","unstructured":"Zaragoza C, Li R-M, Fahle Ga, SH, Fischer, M, Raffeld, AM, Lewis, JB, Kopp (2005) Rab9 GTPase is required for replication of human immunodeficiency virus type 1, filoviruses, and measles virus. J Virol 79:1320\u20131326. https:\/\/doi.org\/10.1128\/JVI.79.18.11742","DOI":"10.1128\/JVI.79.18.11742"},{"key":"13389_CR45","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/nature12205","volume":"497","author":"G Zimmermann","year":"2013","unstructured":"Zimmermann G, Papke B, Ismail S, Vartak N, Chandra A, Hoffmann M, Hahn SA, Triola G, Wittinghofer A, Bastiaens PIH, Waldmann H (2013) Small molecule inhibition of the KRAS-PDE\u03b4 interaction impairs oncogenic KRAS signalling. Nature 497:638\u2013642. https:\/\/doi.org\/10.1038\/nature12205","journal-title":"Nature"}],"container-title":["Applied Microbiology and Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00253-024-13389-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00253-024-13389-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00253-024-13389-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:30:00Z","timestamp":1770294600000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00253-024-13389-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,2]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["13389"],"URL":"https:\/\/doi.org\/10.1007\/s00253-024-13389-8","relation":{},"ISSN":["1432-0614"],"issn-type":[{"value":"1432-0614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,2]]},"assertion":[{"value":"13 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 January 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This article does not contain any studies with human participants or animals performed by any of the authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"1"}}