Modular Supramolecular Polycations Enable Efficient Delivery of Diverse RNA Therapeutics and Vaccines

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.

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Publication Details

Journal
Advanced Materials
Published
2026-02-15
DOI
https://doi.org/10.1002/adma.202513315
Primary Topic
Supramolecular Chemistry and Complexes
Type
article
Field-Weighted Citation Impact
0.00

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article

Modular Supramolecular Polycations Enable Efficient Delivery of Diverse RNA Therapeutics and Vaccines

Andrew M. Howe, Phoebe McCrorie, S J Jones, Ala’ Salem et al.
Advanced Materials
Supramolecular Chemistry and Complexes
article

Modular Supramolecular Polycations Enable Efficient Delivery of Diverse RNA Therapeutics and Vaccines

Andrew M. Howe, Phoebe McCrorie, S J Jones, Ala’ Salem, John S. Tregoning, Cara Moloney, Rafał J. Kopiasz, Alan McIntyre, Roger J. Coulston, Pratik Gurnani, Luke A. Granger, Hadijatou Sallah, Alison Ritchie, Hulya Bayraktutan, Poulam Patel, Francois Hallac, Robin J. Shattock, Robert J. Cavanagh, Anna M. Grabowska, Cameron Alexander, Charalampos Makatsoris, Aimée S. Jeluk, Shreeya Parmar, Ruman Rahman, Lewis O'Shaughnessy, Snjezana Stolnik
article en

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.

Advanced MaterialsVol. 38(16)
Warsaw University of Technology (PL), University of Nottingham (GB), King's College London (GB), Kensington College of Business (GB), Mission Therapeutics (United Kingdom) (GB), Aqdot (United Kingdom) (GB), University College London (GB), Imperial College London (GB), Hacettepe University (TR)
Children's Cancer and Leukaemia Group, National Institute for Health and Care Research, Department of Health and Social Care, Engineering and Physical Sciences Research Council, National Medical Research Council
Good health and well-being
Openalex Percentile: Top 53%
Supramolecular Chemistry and Complexes
DOIOpen Access PDFOpenAlex
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