To celebrate the growth and development of the RSC Applied Polymers community and to highlight the remarkable authors who continue to contribute their high quality work to the journal, we would like to share the opinions and insights of these authors through this introductory blog post. Once dubbed #RSCAppliedfirst50, our blog posts aim to give a voice to the authors behind the research and hope that their insights might shed light upon growing challenges and progress in polymer science and its applications.
In this edition, we hear from Lewis O’Shaughnessy, Rahman Khosravi, James Robins, Akosua Anane-Adjei, Mariarosa Mazza, Naoto Hori, Pratik Gurnani and Cameron Alexander as they discuss their recently published article, ‘Dual end-functionalisation of poly(beta-amino ester) gene delivery vectors using multicomponent chemistry‘.
An introduction from the authors
Delivering mRNA at high efficiency remains a significant challenge in many biomedical settings. In this work we show how we used the Passerini 3-component reaction (P3CR) to diversify the termini of poly(beta-amino ester)s (PBAEs) with the aim of enhancing RNA delivery. We found that changing the end groups of these PBAEs had profound impacts on both their physical and biological properties, with many of the modified polymers proving potent delivery vectors for mRNA.
RNA is an exceptionally useful therapeutic tool, which has already revolutionised our capacity to fight infectious diseases, and could be used for treating many cancers and inherited diseases. So far, RNA has been delivered clinically via lipid nanoparticles, but cationic polymers could also be used as delivery vectors for RNA, especially as polymer-RNA nanoparticles can be much more storage-stable than lipidic systems.
In particular, PBAEs are a class of cationic polymer that have established transfection capability with nucleic acids and are of low toxicity. Previously it has been shown that the polymer end groups in PBAEs can have important effects on the delivery of RNA. In our work, we sought to exploit the P3CR to modify the chain termini with both an aldehyde and an isocyanide at the same time. This allows for the simultaneous introduction of two different substrates into the polymer termini, whilst also allowing access to two previously untapped libraries of substrates for end group modification. And so, in using this reaction, we were able to access previously unexplored areas of chemical space, with a number of our modified polymers demonstrating transfection potency exceeding that of the unmodified PBAE. Additionally, on exposure to cells, polymers modified by the P3CR also exhibited a form of aggregation induced luminescence that we had previously observed in polymers synthesised directly by Passerini 3-component polymerisation.
The natural extension of this work is to continue expanding the polymer library and beginning to elucidate the intricate relationships between polymer structure and the resultant properties of polymer/RNA polyplexes: size, charge, encapsulation efficiency and transfection capability. Ideally such knowledge could lead to more informed polymer design in the future. To enhance our understanding, we’re undertaking computational modelling studies to better visualise how differently modified polymers are each capable of interacting with RNA chains. Beyond this, we hope to further explore the intrinsic luminescence properties of these polymers, and exploit this as an inherent labelling technology to track polyplexes within the cell.
We hope that the findings of this study provide polymer chemists with a powerful tool for rapidly expanding the functional diversity of polymer end groups, allowing for development of a wide range of novel materials. At the same time, we provide additional insights into the science of polymer mediated RNA delivery.
Meet the authors
Lewis O’Shaughnessy
Dr Lewis O’Shaughnessy is a postdoctoral researcher at the University of Nottingham. Having received his MChem degree from the University of Oxford in 2018, he later studied a PhD at the University of Nottingham, researching the synthesis of novel polymers for RNA delivery, from which he graduated in 2025. His current research focuses on the synthesis of supramolecular cationic polymers and their roles as RNA delivery vectors, including work on peptide synthesis, supramolecular polymers and assemblies, and multicomponent polymerisations.
Rahman Khosravi
Dr Rahman Khosravi completed his PhD at the University of Nottingham, where his research focussed on synthesis, formulation and characterisation of nanoparticles for gene delivery, including lipid nanoparticles, polymeric systems and novel polymer-lipid hybrid nanoparticles for mRNA delivery
James Robins
Dr James Robins recently completed his PhD at the University of Nottingham, studying computational biophysics and using computational tools to better understand the structure of polymer-based nanoparticles for the delivery of RNA therapeutics.
Akosua Anane-Adjei
Dr Akosua Anane-Adjei is an Associate Principal Scientist in Pharmaceutical Sciences (Advanced Drug Delivery) at AstraZeneca, Cambridge. She earned her PhD in Advanced Therapeutics and Nanomedicines from the University of Nottingham, investigating polymer–drug conjugates for pancreatic cancer with integrated in vitro/in vivo evaluation and PET CT imaging. Her postdoctoral fellowship at the University of Nottingham focused on controlled radical polymerisation (RAFT), copolymer engineering, and nanoparticle formulation for biomedical applications. Her current work integrates small molecule developability with advanced delivery modalities from early discovery through candidate selection, with emphasis on physicochemical profiling, formulation design, and translational biopharmaceutics.
Mariarosa Mazza
Dr Mariarosa Mazza holds a PhD in Pharmaceutical Sciences from the UCL School of Pharmacy. She is an Associate Director in Advanced Drug Delivery at AstraZeneca (UK), where she leads a team focused on novel modalities, including nucleic acids and polymeric and lipid-based nanoparticles. Her group leverages automation and machine learning to drive system optimisation, supporting a portfolio that spans from oncology cell therapy to gene editing.
Naoto Hori
Dr Naoto Hori is an Assistant Professor of Computational Biophysics in the School of Pharmacy at the University of Nottingham. Naoto received his BSc and MSc in Chemistry from Kobe University. He obtained his PhD in Biophysics at Kyoto university under the supervision of Prof. Shoji Takada. While a postdoctoral researcher with Prof. Dave Thirumalai at the University of Maryland and the University of Texas at Austin, Naoto investigated RNA folding and misfolding mechanisms using molecular simulations. Since joining the University of Nottingham as an independent Nottingham Research Fellow in 2020, he has focused on computational modelling to investigate the complex, heterogeneous structures of long RNA molecules and their therapeutic potential. His work aims to contribute to a broader understanding of RNA biology and develop new approaches to RNA therapeutics using high-performance computing and unique molecular simulation models.
Pratik Gurnani
Dr Pratik Gurnani graduated from the University of Warwick with a Masters in Chemistry in 2014, and continued at the same institution to complete his PhD under the supervision of Prof Sebastien Perrier in 2018, researching new biocompatible nanoparticles for biomedicine applications. Following this, Pratik joined Prof Cameron Alexander’s group as a Research Fellow at the University of Nottingham, developing new manufacturable materials for mRNA vaccines to respond to rapidly respond to global pandemics within the EPSRC Future Vaccines Manufacturing Research Hub. In May 2023 Pratik was appointed as a Lecturer in Pharmaceutical Science at the UCL School of Pharmacy where his research programme is focused on developing novel polymer formulations for RNA therapeutics and vaccines.
Cameron Alexander
Prof. Cameron Alexander is Professor of Polymer Therapeutics and a Fellow of the Royal Society of Chemistry. Following BSc and PhD degrees in Chemistry at the University of Durham, UK, he was a Post-Doctoral Research Fellow at the Melville Laboratory for Polymer Synthesis, University of Cambridge. Cameron was awarded the Royal Society of Chemistry /Society of the Chemical Industry Macro Group UK Prize and Medal in 2014, and the Royal Society of Chemistry Interdisciplinary Prize and Medal 2025 for research at the interface of chemistry, pharmaceutical science and medicine.
Dual end-functionalisation of poly(beta-amino ester) gene delivery vectors using multicomponent chemistry
Lewis O’Shaughnessy, Rahman Khosravi, James Robins, Akosua Anane-Adjei, Mariarosa Mazza, Naoto Hori, Pratik Gurnani and Cameron Alexander
RSC Appl. Polym., 2026, 4, 432-450. DOI: 10.1039/D5LP00251F
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