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Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
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High-Throughput Automation of Endosomolytic Polymers for mRNA Delivery
David Ulkoski1, Michael J Munson2, Max E Jacobson3
1Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Boston 02451, United States.
ACS Applied Bio Materials
|January 11, 2022
Summary
Researchers developed new polymers for effective messenger RNA (mRNA) delivery. Shorter side chains and higher cationic density improved mRNA encapsulation, with one polymer showing superior transfection compared to traditional methods.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Drug Delivery Systems
Background:
- Growing interest in RNA-based therapeutics necessitates efficient delivery systems.
- Current methods for evaluating polymeric delivery materials are time-consuming.
Purpose of the Study:
- To synthesize and screen novel copolymers for messenger RNA (mRNA) delivery.
- To establish a high-throughput workflow for rapid assessment of polymer performance.
- To elucidate structure-activity relationships for optimized mRNA delivery.
Main Methods:
- Synthesis of copolymers using dimethylaminoethyl methacrylate (DMAEMA) or diethylaminoethyl methacrylate (DEAEMA) with varying alkyl methacrylate monomers.
- Development of a high-throughput workflow for evaluating mRNA encapsulation and transfection.
- Cytotoxicity and transfection efficiency assays were performed.
Main Results:
- mRNA encapsulation efficiency increased with higher cationic density and shorter alkyl chains (2-6 carbons).
- DEAEMA-co-BMA (EB) polyplexes showed minimal cytotoxicity up to 18 hours.
- The lowest molecular weight polymer (EB10,250) demonstrated superior transfection compared to polyethyenimine (PEI).
Conclusions:
- The developed high-throughput approach accelerates the screening of polymeric systems for mRNA delivery.
- Optimized copolymers, particularly EB10,250, show significant potential for enhancing mRNA therapeutic efficacy.
- This platform can be generalized for assessing various materials in mRNA delivery applications.
