Modular supramolecular polycations enable efficient delivery of diverse RNA therapeutics and vaccines
File(s)
Accepted version
Supporting information
Author(s)
Type
Journal Article
Abstract
We describe a modular, diverse, and customizable supramolecular-materials platform that can deliver nucleic acids in vitro and in vivo. The chemistries deployed enable the generation of multiple supramolecular polycations, which can associate with RNA to form polyelectrolyte complexes, but which have the unique feature of reversible cross-links, via host–guest interactions of monomers that display aromatic amino acid termini with cucurbit[8]uril (CB[8]). Families of supramolecular polymers can be prepared by simple variation in monomer structure, enabling the tuning of properties. We demonstrate that these supramolecular polyelectrolyte complexes with RNA can be prepared easily via automatable procedures to generate nanoparticles that meet Critical Quality Attributes for manufactured RNA vaccines and therapeutics. We show that these materials can deliver RNA to a range of cell types, displaying reporter-protein expression at levels equivalent to, or greater than, commercial transfection reagents, with no acute adverse phenotypic effects. Finally, we demonstrate the success of our materials platform across a range of nucleic acid types, with expression of mRNA within tumors of an orthotopic Triple-Negative Breast Cancer mouse model, knockdown of a kinase implicated in cancer progression via siRNA, and effective protection against H1N1 influenza virus challenge in mice following injections of self-amplifying RNA.
Date Issued
2026-03-17
Date Acceptance
2026-02-02
Citation
Advanced Materials, 2026, 38 (16)
ISSN
0935-9648
Publisher
Wiley
Journal / Book Title
Advanced Materials
Volume
38
Issue
16
Copyright Statement
Copyright © 2026 Wiley-VCH GmbH. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41691403
Subjects
RNA therapeutics and vaccines
breast cancer
gene delivery
influenza
supramolecular materials
Publication Status
Published
Coverage Spatial
Germany
Article Number
e13315
Date Publish Online
2026-02-15