Biologically engineered vectors enable topical mRNA delivery for skin regeneration

Biologically engineered vectors enable topical mRNA delivery for skin regeneration | 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 Article Biologically engineered vectors enable topical mRNA delivery for skin regeneration Nicolas Grandchamp, Julie Gerard, Heloise Pilet, Charbel Bouez, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9293588/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 Messenger RNA (mRNA) therapeutics enable transient protein expression without altering the cellular genome, making them attractive for regenerative medicine. However, efficient and safe delivery to the skin is still challenging. Lipid nanoparticles (LNPs) have enabled major advances in RNA delivery, but in skin their performance is often limited by tissue accessibility, formulation constraints and local tissue responses. In parallel, biologically assembled delivery systems - including viral vectors, engineered extracellular vesicles and virus-like particles - have expanded, but remain constrained by challenges in cargo control, particle heterogeneity and biosafety, while lacking a unified conceptual framework. Here we introduce Biologically Engineered Vectors (BEVs) as a class of biologically assembled delivery particles generated through genetic or cellular engineering to transport therapeutic nucleic acids. Within this class, we developed reverse-transcription-deficient BEVs (rtBEVs) derived from lentiviral particles engineered to prevent RNA-to-DNA conversion and genomic integration. rtBEVs efficiently delivered functional mRNA to keratinocytes, induced protein expression throughout reconstructed epidermis after topical administration, and improved the histological quality of repair relative to mRNA-loaded LNPs in a diabetic rat wound model. Biological sciences/Biotechnology/Gene delivery Health sciences/Molecular medicine Full Text Additional Declarations Yes there is potential Competing Interest. N.G. and H.P. are inventors on a pending patent application assigned to GEG Tech covering RNA sequences relevant to this work. N.G. is also an inventor on a granted patent assigned to GEG Tech covering reverse transcriptase mutations relevant to the rtBEV technology described here. GEG Tech partially funded this study. The other authors declare no competing interests. Supplementary Files SupplementaryMaterials.pdf Dataset 1 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-9293588","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":618417423,"identity":"22cd463a-e774-491f-9ed9-ed578a8b79e2","order_by":0,"name":"Nicolas Grandchamp","email":"data:image/png;base64,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","orcid":"","institution":"GEG TECH","correspondingAuthor":true,"prefix":"","firstName":"Nicolas","middleName":"","lastName":"Grandchamp","suffix":""},{"id":618417424,"identity":"49caa2c9-8446-4568-a2e4-72a7d0dba3f6","order_by":1,"name":"Julie Gerard","email":"","orcid":"","institution":"GEG Tech","correspondingAuthor":false,"prefix":"","firstName":"Julie","middleName":"","lastName":"Gerard","suffix":""},{"id":618417425,"identity":"1ec3ba1d-aa3b-45f6-b760-b2ff3edcdc67","order_by":2,"name":"Heloise Pilet","email":"","orcid":"","institution":"GEG Tech","correspondingAuthor":false,"prefix":"","firstName":"Heloise","middleName":"","lastName":"Pilet","suffix":""},{"id":618417426,"identity":"c65b2a06-c0d3-42a8-a7a1-4e85638cf884","order_by":3,"name":"Charbel Bouez","email":"","orcid":"","institution":"IFF","correspondingAuthor":false,"prefix":"","firstName":"Charbel","middleName":"","lastName":"Bouez","suffix":""},{"id":618417427,"identity":"cd471c80-9a4d-403d-bda5-42d8d2ef5bf1","order_by":4,"name":"Xu Du","email":"","orcid":"","institution":"School of Pharmacy, Nantong University","correspondingAuthor":false,"prefix":"","firstName":"Xu","middleName":"","lastName":"Du","suffix":""},{"id":618417428,"identity":"3de8b00d-6f2e-43e8-8b96-76d268809534","order_by":5,"name":"Yong Chen","email":"","orcid":"","institution":"School of Pharmacy, Nantong University","correspondingAuthor":false,"prefix":"","firstName":"Yong","middleName":"","lastName":"Chen","suffix":""},{"id":618417429,"identity":"5f240133-851c-4866-aed0-64ab504b462f","order_by":6,"name":"Yogeshvar Kalia","email":"","orcid":"https://orcid.org/0000-0001-9049-5489","institution":"University of Geneva","correspondingAuthor":false,"prefix":"","firstName":"Yogeshvar","middleName":"","lastName":"Kalia","suffix":""},{"id":618417430,"identity":"5530f2d3-9eee-4cad-a41f-003770530212","order_by":7,"name":"Pascal Clayette","email":"","orcid":"","institution":"GEG Tech","correspondingAuthor":false,"prefix":"","firstName":"Pascal","middleName":"","lastName":"Clayette","suffix":""},{"id":618417431,"identity":"ed751063-6003-408b-86ac-9f827d2601a3","order_by":8,"name":"Bruno Bernard","email":"","orcid":"","institution":"GEG Tech","correspondingAuthor":false,"prefix":"","firstName":"Bruno","middleName":"","lastName":"Bernard","suffix":""}],"badges":[],"createdAt":"2026-04-01 15:05:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9293588/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9293588/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107707167,"identity":"4fd8e66b-da08-4602-8f4e-8387b3e1eb41","added_by":"auto","created_at":"2026-04-24 09:19:41","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1692970,"visible":true,"origin":"","legend":"Article File","description":"","filename":"J.Gerardetal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9293588/v1_covered_60c24d92-0be6-4a27-8f71-d54b06f24eae.pdf"},{"id":107593144,"identity":"1de0af70-663a-419d-bb65-c5f1c5de764f","added_by":"auto","created_at":"2026-04-23 04:00:47","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":23064863,"visible":true,"origin":"","legend":"Dataset 1","description":"","filename":"SupplementaryMaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9293588/v1/4c702f9e7dc6ffe5a4976c04.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nN.G. and H.P. are inventors on a pending patent application assigned to GEG Tech covering RNA sequences relevant to this work. 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