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Updated: Jun 12, 2026
Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
Synthesis of Amphiphilic Cationic Poly(β-amino acid) Derivatives and Their PEG Length Optimization for mRNA
Sung Been Lim1, Jun Su An1, DongHyun Kang1
1Department of Biological Sciences and Bioengineering, Inha University, 100 Inha-ro, Michuhol-gu, Incheon 22212, Republic of Korea.
Abstract:
We synthesized a series of amphiphilic cationic poly(ethylene glycol)-b-poly(β-amino acid) derivatives with various lengths of PEG to investigate the effects of PEG lengths on mRNA transfection. The surface charges of the polyplexes with a DPOEG ≥ 4 gradually decreased as DPOEG increased. This indicated that hydrophilic PEG with a DPOEG ≥ 4 was exposed on the surface of the polyplexes, which was further confirmed using 1H NMR. Polyplexes with a DPOEG ≤ 4 exhibited mRNA transfection efficacy similar to that of homopolymers. However, the transfection efficacy of the polyplex with a DPOEG ≥ 12 markedly decreased, mainly because of the decreased cellular uptake and stability of the polyplexes against serum albumin. This indicated that the PEG length considerably affected the delivery efficacy of IVT mRNA. Our results provide useful information for the fundamental polymer design to optimize the PEG length of amphiphilic cationic polymers for systemic IVT mRNA delivery.
