Manu on Lenti G2B Gene Therapy for β-Thalassemia

Manu on Lenti G2B Gene Therapy for β-Thalassemia | 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 Manu on Lenti G2B Gene Therapy for β-Thalassemia Xiao-Bing Zhang, zhuying Gao, Zhi-Xue Yang, Dong-Hao Deng, Feng Zhang, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4249953/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract Gene therapy, particularly lentiviral vector-based approaches, has emerged as a crucial alternative for treating β-thalassemia, one of the most prevalent monogenic disorders worldwide. This study focuses on overcoming clinical challenges associated with existing HBB lentiviral vectors, characterized by suboptimal titers and inadequate β-globin expression. We have advanced the BB305 lentiviral vector, creating a novel HBB vector, G2B, specifically engineered for β-thalassemia gene therapy. The optimization involved refining the Locus Control Region (LCR) sequence length and incorporating mutated gamma globin HGB2 promoter into the BB305 vector. Our innovative G2B vector exhibits a significant ~4-fold increase in lentiviral titer and a 50% enhancement in β-globin expression compared to the clinical BB305 vector. In the Hbbth4/Hbb+ thalassemic hematopoietic stem/progenitor cell transplantation model, the G2B vector demonstrated remarkable therapeutic efficacy without altering integration safety profiles. These findings highlight the potential of the G2B vector in treating β-thalassemia and possibly other hemoglobinopathies. Our research offers a promising pathway toward more effective and affordable gene therapy options for β-thalassemia and similar genetic disorders. Health sciences/Diseases/Haematological diseases Biological sciences/Stem cells/Haematopoietic stem cells β-thalassemia Hemoglobin Subunit Beta (HBB) Gene therapy Lentiviral vector Locus Control Region (LCR) Integration Safety Hemoglobinopathie Full Text Additional Declarations There is NO conflict of interest to disclose. Supplementary Files SupplementaryMaterialsforLentiG2Bmanu.pdf Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: revise 10 Jun, 2024 Review # 1 received at journal 29 May, 2024 Review # 2 received at journal 23 May, 2024 Reviewer # 2 agreed at journal 18 May, 2024 Reviewer # 1 agreed at journal 07 May, 2024 Reviewers invited by journal 21 Apr, 2024 Editor assigned by journal 12 Apr, 2024 Submission checks completed at journal 12 Apr, 2024 First submitted to journal 10 Apr, 2024 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. 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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-4249953","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":293609349,"identity":"986480bf-1b31-4b56-889f-10ba85ca6be8","order_by":0,"name":"Xiao-Bing 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