Model-based characterization of metabolism of the recombinant adeno-associated virus (rAAV) production via Human Embryonic Kidney (HEK293) cells

preprint OA: closed CC-BY-4.0
📄 Open PDF Full text JSON View at publisher

Abstract

Abstract In this study, we present a kinetic-metabolic model describing adeno-associated virus (AAV) production via Hek293 cells, encompassing the main metabolic pathways, namely glycolysis, tricarboxylic acid cycle (TCA), pyruvate fates, the pentose phosphate pathway, anaplerotic reaction, amino acid metabolism, nucleotides synthesis, biomass synthesis and the metabolic pathways of protein synthesis of AAV (capsid and Rep proteins). For the modelling, Michaelis-Menten kinetic is assumed to define the metabolic model. A dataset from bioreactor cultures containing metabolite profiles of adeno-associated virus 6 (AAV6) production via triple transient transfection at low cell density culture, including concentration profiles of glutamine, glutamic acid, glucose, lactate, and ammonium, is utilized for fitting and computing the model parameters. The model resulting from the adjusted parameters well defines the experimental data. Subsequently, a Sobol-based global sensitivity analysis procedure is applied to determine the most sensitive parameters in the final model.
Full text 10,443 characters · extracted from preprint-html · click to expand
Model-based characterization of metabolism of the recombinant adeno-associated virus (rAAV) production via Human Embryonic Kidney (HEK293) cells | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Model-based characterization of metabolism of the recombinant adeno-associated virus (rAAV) production via Human Embryonic Kidney (HEK293) cells Somaiyeh Khodadadi Karimvand, Miroslava Cuperlovic-Culf, Amine A. Kamen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4594915/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract In this study, we present a kinetic-metabolic model describing adeno-associated virus (AAV) production via Hek293 cells, encompassing the main metabolic pathways, namely glycolysis, tricarboxylic acid cycle (TCA), pyruvate fates, the pentose phosphate pathway, anaplerotic reaction, amino acid metabolism, nucleotides synthesis, biomass synthesis and the metabolic pathways of protein synthesis of AAV (capsid and Rep proteins). For the modelling, Michaelis-Menten kinetic is assumed to define the metabolic model. A dataset from bioreactor cultures containing metabolite profiles of adeno-associated virus 6 (AAV6) production via triple transient transfection at low cell density culture, including concentration profiles of glutamine, glutamic acid, glucose, lactate, and ammonium, is utilized for fitting and computing the model parameters. The model resulting from the adjusted parameters well defines the experimental data. Subsequently, a Sobol-based global sensitivity analysis procedure is applied to determine the most sensitive parameters in the final model. Adeno-associated viruses Michaelis-Menten kinetic Metabolic model Global Sensitivity analysis Optimization Model fitting Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4594915","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":323515511,"identity":"4abf33d3-267d-411e-bc72-677e36da9608","order_by":0,"name":"Somaiyeh Khodadadi Karimvand","email":"","orcid":"","institution":"University of Ottawa","correspondingAuthor":false,"prefix":"","firstName":"Somaiyeh","middleName":"Khodadadi","lastName":"Karimvand","suffix":""},{"id":323515512,"identity":"ed1e1e8d-b20a-48a5-ac1d-0965c24f42f2","order_by":1,"name":"Miroslava Cuperlovic-Culf","email":"","orcid":"","institution":"National Research Council Canada","correspondingAuthor":false,"prefix":"","firstName":"Miroslava","middleName":"","lastName":"Cuperlovic-Culf","suffix":""},{"id":323515513,"identity":"eb8253e3-fc42-4e41-b13d-bd262e6a76a7","order_by":2,"name":"Amine A. Kamen","email":"","orcid":"","institution":"McGill University","correspondingAuthor":false,"prefix":"","firstName":"Amine","middleName":"A.","lastName":"Kamen","suffix":""},{"id":323515514,"identity":"5bb40f97-b80c-4a10-b54d-ef6f20b5e762","order_by":3,"name":"Miodrag Bolic","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBUlEQVRIie3PMUsDMRTA8XcUcsv7AC3I9SskFAJFbD7LcYOLuzecJcdBXU5nB/FLCJ1zBHJLwbWlu5ODU6koYlLORUzbUTD/KcP7JXkAodAfjGqAvjsI6EkF+RFk/E2YjCxZACA5QITqCFWRhGh2BOFtr1nnxRWw67JUbw86EcPqub+FydBLNMnGC9OCwEY2N3M9QkL4oIaMSS9BPpDEALtLpY7mOq0J8CWC++fv0R35NECXjtw7Em9WH6DEXlLOio5IR5Cv7Supn9hdyluFrLa71OZ8hObi8v2EZpmXPOlmJTfTRMSVft0Wp0lctY/sJZ+c+UiXxp9X7Z+3TQ9OhEKh0D/uC3QCXhnLxVNkAAAAAElFTkSuQmCC","orcid":"","institution":"University of Ottawa","correspondingAuthor":true,"prefix":"","firstName":"Miodrag","middleName":"","lastName":"Bolic","suffix":""}],"badges":[],"createdAt":"2024-06-17 14:56:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4594915/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4594915/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":59987058,"identity":"a7a2953d-1d0c-4030-8f70-2dffeb0bda41","added_by":"auto","created_at":"2024-07-10 07:32:18","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":855351,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4594915/v1_covered_bfb56f3e-b76c-4a68-9be5-80f6c3886033.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Model-based characterization of metabolism of the recombinant adeno-associated virus (rAAV) production via Human Embryonic Kidney (HEK293) cells","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Adeno-associated viruses, Michaelis-Menten kinetic, Metabolic model, Global Sensitivity analysis, Optimization, Model fitting","lastPublishedDoi":"10.21203/rs.3.rs-4594915/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4594915/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn this study, we present a kinetic-metabolic model describing adeno-associated virus (AAV) production via Hek293 cells, encompassing the main metabolic pathways, namely glycolysis, tricarboxylic acid cycle (TCA), pyruvate fates, the pentose phosphate pathway, anaplerotic reaction, amino acid metabolism, nucleotides synthesis, biomass synthesis and the metabolic pathways of protein synthesis of AAV (capsid and Rep proteins). For the modelling, Michaelis-Menten kinetic is assumed to define the metabolic model. A dataset from bioreactor cultures containing metabolite profiles of adeno-associated virus 6 (AAV6) production via triple transient transfection at low cell density culture, including concentration profiles of glutamine, glutamic acid, glucose, lactate, and ammonium, is utilized for fitting and computing the model parameters. The model resulting from the adjusted parameters well defines the experimental data. Subsequently, a Sobol-based global sensitivity analysis procedure is applied to determine the most sensitive parameters in the final model.\u003c/p\u003e","manuscriptTitle":"Model-based characterization of metabolism of the recombinant adeno-associated virus (rAAV) production via Human Embryonic Kidney (HEK293) cells","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-09 11:18:07","doi":"10.21203/rs.3.rs-4594915/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"220c4d52-1a46-44d1-af4f-3a04cef612c3","owner":[],"postedDate":"July 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-10T07:24:10+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-09 11:18:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4594915","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4594915","identity":"rs-4594915","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2024) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00
unpaywall
last seen: 2026-05-22T02:00:06.705733+00:00
License: CC-BY-4.0