دورية أكاديمية
High-Throughput Automation of Endosomolytic Polymers for mRNA Delivery.
| العنوان: | High-Throughput Automation of Endosomolytic Polymers for mRNA Delivery. |
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| المؤلفون: | Ulkoski D; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Boston 02451, United States., Munson MJ; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg SE-431 83, Sweden., Jacobson ME; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee 37212, United States., Palmer CR; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee 37212, United States., Carson CS; Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37240-0002, United States., Sabirsh A; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg SE-431 83, Sweden., Wilson JT; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee 37212, United States.; Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37240-0002, United States., Krishnamurthy VR; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Boston 02451, United States. |
| المصدر: | ACS applied bio materials [ACS Appl Bio Mater] 2021 Feb 15; Vol. 4 (2), pp. 1640-1654. Date of Electronic Publication: 2021 Jan 19. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: ACS Publications Country of Publication: United States NLM ID: 101729147 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2576-6422 (Electronic) Linking ISSN: 25766422 NLM ISO Abbreviation: ACS Appl Bio Mater Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : ACS Publications, [2018]- |
| مواضيع طبية MeSH: | Gene Transfer Techniques/*standards , Genetic Therapy/*methods , Polymers/*chemistry , RNA, Messenger/*metabolism |
| مستخلص: | In recent years, there has been an increasing interest in designing delivery systems to enhance the efficacy of RNA-based therapeutics. Here, we have synthesized copolymers comprised of dimethylaminoethyl methacrylate (DMAEMA) or diethylaminoethyl methacrylate (DEAEMA) copolymerized with alkyl methacrylate monomers ranging from 2 to 12 carbons, and developed a high throughput workflow for rapid investigation of their applicability for mRNA delivery. The structure activity relationship revealed that the mRNA encapsulation efficiency is improved by increasing the cationic density and use of shorter alkyl side chains (2-6 carbons). Minimal cytotoxicity was observed when using DEAEMA- co -BMA (EB) polyplexes up to 18 h after dosing, independent of a poly(ethylene glycol) (PEG) first block. The lowest molecular weight polymer (EB10,250) performed best, exhibiting greater transfection than polyethyenimine (PEI) based upon the number of cells transfected and mean intensity. Conventional investigations into the performance of polymeric materials for mRNA delivery is quite tedious, consequently limiting the number of materials and formulation conditions that can be studied. The high throughput approach presented here can accelerate the screening of polymeric systems and paves the way for expanding this generalizable approach to assess various materials for mRNA delivery. |
| فهرسة مساهمة: | Keywords: DEAEMA polymers; DMAEMA; RNA therapeutics; high-throughput screening; mRNA delivery; polyplexes |
| المشرفين على المادة: | 0 (Polymers) 0 (RNA, Messenger) |
| تواريخ الأحداث: | Date Created: 20220111 Date Completed: 20220328 Latest Revision: 20230424 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1021/acsabm.0c01463 |
| PMID: | 35014512 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 2576-6422 |
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| DOI: | 10.1021/acsabm.0c01463 |