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Polyanion chemistry engineers ternary RNA nanoparticle structure-function from the inside-out
L Hu*, DJ Peeler*, T Jin, J Doutch, B Shao, J Yeow, L Ma, H Barriga, J Tang, X Cao, C Liu, C Grigsby, A Alexander-Katz, RJ Shattock, MM Stevens. under review
We’re developing polymer-based alternatives to lipid nanoparticles by engineering polyanions to shape RNA-loaded nanoparticles from the inside out. By tuning PEG architectures and polyanion chemistry, we found a sweet spot that creates tiny, pH-responsive particles that stay stable outside cells but still release their RNA cargo effectively. Using high-throughput assays, neutron scattering, and molecular simulations, we uncovered how these polymers control structure, protein interactions, and ultimately transfection performance. This first work lays out a clear design framework for building responsive, targetable RNA delivery systems with cationic and anionic polyelectrolyte blends.
Nanoscale biodegradable printing for designed tuneability of vaccine delivery kinetics
DJ Peeler*, R Sun*, C Kutahya, P Peschke, K Zhou, G Brachi, J Yeow, O Rifaie-Graham, JP Wojciechowski, T Fernandez-Debets, V LaLone, X Song, K Polra, PF McKay, JS Tregoning, RJ Shattock, MM Stevens (2025) Advanced Materials, https://doi.org/10.1002/adma.202417290
We introduce a novel family of PLGA-based resins for two-photon polymerization 3D printing, Spatiotemporal Controlled Release Inks of Biocompatible polyEsters (SCRIBE), and show how precise, top-down microparticle engineering can tune immune responses to encapsulated vaccines.
The role of helper lipids in optimising nanoparticle formulations of self-amplifying RNA
BD Barbieri, DJ Peeler, K Samnuan, S Day, K Hu, HJ Sallah, JS Tregoning, PF McKay, RJ Shattock. (2024) Journal of Controlled Release 374:280-292. link
We demonstrated that human skin explants can be used to discriminate helper lipid-enhanced transfection of LNP-saRNA. Besides helper lipid effects, we also observed ionizable lipid-dependent immune responses in primary human PBMCs that differed from those of a commonly used monocyte cell line.
Lytic polyplex vaccines enhance antigen-specific cytotoxic T cell response through induction of local cell death
DJ Peeler*, A Yen*, N Luera, PS Stayton, SH Pun. (2021) Advanced Therapeutics, 4(8):2100005. link
We adapted a vector initially used for plasmid delivery to investigate how endosomal escape mediated by lytic peptides can augment anti-cancer cellular immunity generated by peptide antigen and TLR3 agonist delivery.
pH-sensitive polymer micelles provide selective and potentiated lytic capacity to venom peptides for effective intracellular delivery
DJ Peeler, SN Thai, YL Cheng, PJ Horner, DL Sellers, SH Pun. (2019) Biomaterials, 192: 235-244. link
We synthesized and screened dozens of lytic peptides and evaluated their ability to enhance endosomal escape and pDNA transfection in the brain when conjugated to a pH-responsive di-block copolymer.
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Invited talks
Invited talks
5. DJ Peeler, Z Wang, S Jokonya, C Thomas, M Briones Ortas, PF McKay, JS Tregoning, RJ Shattock, PS Stayton, MM Stevens. “Targeted STING agonism intersects with self-amplifying RNA immunogenicity through formulation-specific innate intermediates” 11th International Oligo Symposia: Antisense and Therapeutic Nucleic Acids, Oxford, UK 2025 and CRS Annual Meeting & Expo, Philadelphia, PA 2025
4. DJ Peeler, S Jokonya, Z Wang, JS Tregoning, RJ Shattock, PS Stayton, MM Stevens. "Location, Location, Inflammation: Targeted STING agonism differentially impacts expression and immunogenicity of self-amplifying RNA formulated in polymer vs. lipid nanoparticles" Drug Carriers in Medicine & Biology Gordon Research Conference, Portland, Maine 2024 and RNA Vaccines and Therapeutics Conference, London, UK 2024
3. DJ Peeler “Soft Materials for Drug Delivery: from Nano to Micro” Oxford Life Science Alliance Annual Symposium 2024
2. DJ Peeler*, R Sun*, G Brachi, C Kutahya, K Zhou, J Yeow, O Rifaie-Graham, X Song, BD Barbieri, K Polra, J Tregoning, R Shattock, MM Stevens “Injectable hollow microparticles with high macromolecule loading and design-controlled release” Gordon Research Seminar: Drug Carriers in Medicine & Biology 2022
1. DJ Peeler, SN Thai, YL Cheng, PJ Horner, DL Sellers, SH Pun. " Lytic peptide polymer properties that promote endosomal escape of nucleic acid cargo" Oligonucleotide Therapeutics Society 2018 Annual Meeting
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