Poster Presentation Royal Australian Chemical Institute National Congress 2026

Radial dendronised polymers for gene delivery. (#425)

Cooper M Kyrwood 1 2 , Marck Norret 1 2 , Cameron Evans 2 3 , Iyer Swaminathan 1 2
  1. University of Western Australia, Perth, WA, Australia
  2. ARC Training Centre of Biomedical Analysis, Perth, WA, Australia
  3. University of Tasmania, Hobart, TAS, Australia

Dendronised polymers are a unique class of cationic polymer which have outcompeted a commercial liposomal reagent in gene delivery(1). Cationic polymers represent a distinct modality of gene therapy, distinct from the massively-popular lipid nanoparticles (LNPs) which have swept the field in light of the Covid-19 pandemic. However, cationic polymers have many properties which confer them with unique advantages in comparison with LNPs; most notably of which is their functionalisation capacity. Dendronised polymers dial this to the max; building on the work of Tomalia's famous dendrimers(2), dendronised polymers are typically thought of as linear polymers with hyperbranched dendrimer-like side-chains(1,3). Our poly(amidoamine) (PAMAM)-based dendronised polymers present a nigh-innumerable amount of cationic amine surface groups which allow for nucleic acid condensation, cellular uptake, and make for potential sites of functionalisation.  In this work, we have synthesised an as-yet unseen subclass comprising ‘radial’ dendronised polymers. We have investigated a library of this subclass for in vitro gene delivery of multiple genetic cargoes and present the results of that work herein.

  1. Kretzmann, Jessica A., et al. “Synthetically Controlling Dendrimer Flexibility Improves Delivery of Large Plasmid DNA.” Chemical Science, vol. 8, no. 4, Mar. 2017, pp. 2923–30. pubs.rsc.org, https://doi.org/10.1039/C7SC00097A.
  2. Tomalia, Donald A. “Dendrimers, Dendrons, and the Dendritic State: Reflection on the Last Decade with Expected New Roles in Pharma, Medicine, and the Life Sciences.” Pharmaceutics, vol. 16, no. 12, Nov. 2024, p. 1530. DOI.org (Crossref), https://doi.org/10.3390/pharmaceutics16121530.
  3. Evans, Cameron W., et al. “Intracellular Communication between Synthetic Macromolecules.” Journal of the American Chemical Society, vol. 144, no. 31, Aug. 2022, pp. 14112–20. DOI.org (Crossref), https://doi.org/10.1021/jacs.2c02793.