Related Experiment Video

Updated: Sep 21, 2025

Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
08:29

Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA

Published on: February 1, 2019

10.2K

Random Copolymers of Lysine and Isoleucine for Efficient mRNA Delivery

Iuliia Pilipenko1,2, Olga Korovkina1, Nina Gubina1

  • 1Institute of Chemistry, St. Petersburg State University, Universitetskii pr. 26, Peterhof, 198504 St. Petersburg, Russia.

International Journal of Molecular Sciences
|May 28, 2022
PubMed

Insights

New random polypeptides effectively deliver messenger RNA (mRNA) therapeutics. These carriers protect mRNA from degradation, enhance cellular uptake, and show lower toxicity, offering a promising solution for mRNA delivery applications.

Area of Science:

  • Biotechnology
  • Polymer Chemistry
  • Molecular Medicine

Background:

  • Messenger RNA (mRNA) therapeutics offer potential for disease prevention and treatment.
  • Effective delivery systems are crucial for mRNA stability, cellular uptake, and release.
  • Existing delivery vectors face challenges in protection, toxicity, and transfection efficiency.

Purpose of the Study:

  • To synthesize and evaluate random poly(lysine-co-isoleucine) polypeptides as novel carriers for mRNA delivery.
  • To optimize the encapsulation of mRNA into polyplexes using these copolymers.
  • To assess the efficacy and safety of these polypeptide-based mRNA delivery systems.

Main Methods:

  • Synthesis of random poly(lysine-co-isoleucine) copolymers with varying monomer ratios.
  • Characterization of polyplexes formed between mRNA and copolymers (size, ζ-potential, encapsulation efficacy).
  • Evaluation of mRNA protection against ribonuclease, cytotoxicity, and in vitro transfection efficiency.

Main Results:

  • Poly(lysine-co-isoleucine) with an 80/20 ratio yielded polyplexes with small size, positive ζ-potential, and >90% mRNA encapsulation.
  • The phase inversion method proved optimal for mRNA encapsulation into polyplexes.
  • Copolymers demonstrated effective mRNA protection from ribonuclease and reduced toxicity compared to lysine homopolymers.
  • Poly(lysine-co-isoleucine) showed superior transfection efficacy compared to poly(ethyleneimine) for GFP and luciferase mRNAs.

Conclusions:

  • Random poly(lysine-co-isoleucine) copolymers are effective and promising candidates for mRNA delivery.
  • The developed delivery system offers enhanced mRNA protection, reduced toxicity, and improved transfection efficiency.
  • These findings support the advancement of polypeptide-based carriers for therapeutic mRNA applications.
Keywords:
cationic polypeptidesmRNA deliverypolyplexesrandom amphiphilic copolymerstransfection

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