Advanced healthcare materialsMay 16, 2018

New Polymer Materials for Delivering mRNA Without Viruses in Lab and Animal Tests

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 2, 2026

Abstract

The most stable terpolymer shows transfection efficacy several times higher than polyethylenimine when injected intravenously in mice.

Novel ionizable terpolymers were designed using a combination of specific polymerization techniques.
The ability to deliver mRNA is influenced by the material's physiochemical properties, including lipophilicity.
Formulation methods for complexing the polymer with oligonucleotides are identified as a previously unstudied factor in nucleic acid delivery.
The terpolymer's focused delivery to the spleen suggests potential applications in cancer immunotherapy and vaccination.

Simplified

The production of new proteins with messenger RNA (mRNA) has gained a broad interest due to its potential for addressing a wide range of diseases. Here, the design and characterization of novel ionizable poly(β-amino ester)-co-poly(caprolactone) terpolymers, synthesized via the combination of the ring opening polymerization and the Michael step-growth polymerization, are reported. The versatility of this method is demonstrated by varying the number of caprolactone units attached to each poly(β-amino ester) (PBAE) terpolymer. The ability of the novel poly-caprolactone (PCL)-based PBAE materials to deliver mRNA is shown to depend on the physiochemical characteristics of the material, such as lipophilicity, as well as the formulation method used to complex the polymer with the oligonucleotide. This latter variable represents a previously unstudied aspect of PBAE library screens that can play an important role in identifying true top candidates for nucleic acid delivery. The most stable terpolymer is injected intravenously (IV) in mice and shows a transfection efficacy several times higher than the polyethylenimine (PEI) which is focused in the spleen, opening the possibility to use these biodegradable carriers in the intravenous delivery of antigen-encoding mRNA for cancer immunotherapy and vaccination.

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New Polymer Materials for Delivering mRNA Without Viruses in Lab and Animal Tests

Abstract

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