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RESEARCH / LITERATURE

Research Literature

Find research, methods, and reviews across our scientific fields.

One collection · Original publication dates · Authors, journals & DOIs

All publications 147

Duplicate DOIs are merged. This is a selected collection, not an exhaustive bibliography.

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Methods
Journal of Controlled Release

Uncovering the influence of lyoprotection on stability of mRNA-LNPs after lyophilization and high temperature storage

Zixuan Zhen; Mittal Darji; Kuo-Chih Shih; Xinhao Lin; Rama Prajapati; Sheyda Ranjbar; Nirnoy Dan; Grace Shenouda; Jonathan Hu; Robin Bogner; Xiuling Lu

Researchers compared 12 lyophilized mRNA-LNP formulations containing sucrose, trehalose, and polyvinylpyrrolidone. A ternary protectant system at a 1:20 lipid-to-protectant ratio preserved particle properties, RNA integrity, and in vitro transfection after one month at 40°C. Sucrose crystallization reduced protection. The results show why physical measurements need functional confirmation and do not establish a clinical product shelf life.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1016/j.jconrel.2026.115412

Original research
ACS nano

Lipid Nanoparticle Surface Engineering with Heparosan Polysaccharides Enhances mRNA Efficacy via Reduced Endosomal Retention

Yuxin He; Lin Wang; Abigael P. Williams; Trisha I. Valerio; Yuanhong Sun; James Bowman; Samantha D. Ricketts; Savannah Hammond; Aidan Sison; Jezan Alexandre; Zachary Niastor; Wei R. Chen; Dixy E. Green; Kar-Ming Fung; Paul L. DeAngelis; Stefan Wilhelm

Heparosan surface modification was compared with conventional PEG-based nanoparticles across several ionizable lipid formulations. Modified particles improved expression in immune-cell models and showed reduced association with late endosomes and lysosomes. Mouse experiments assessed repeated expression and vaccine antibody responses. The findings support an alternative surface-engineering approach, while long-term immunogenicity, biodistribution, and manufacturing consistency require additional study.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1021/acsnano.6c11865

Methods
ACS Central Science

Room Temperature Structures of Solvated Organic Molecules Enabled by Liquid Cell Electron Diffraction

Niko W. Vlahakis; Krzysztof Konieczny; Cameron W. Flowers; Miguel A. Garcia-Garibay; Jose A. Rodriguez

Liquid cells made from paired carbon grids retained a thin solution layer around microcrystals for room-temperature MicroED. The study obtained atomic structures from solvated organic molecules and pharmaceutical hydrates while using low-dose, rapid, multi-crystal acquisition to limit beam damage. It extends access to hydrated or solvated states, but sample-specific radiation sensitivity and preparation remain important constraints.

MicroED structure determination
Read guide →Original paper ↗

DOI: 10.1021/acscentsci.6c00603

Original research
Nature biomedical engineering

Microfluidics-mediated spatial control of mRNA lipid nanoparticles primes translation and enhances vaccine potency

Zhouyi Zheng; Yue Jiang; Yue Gong; Qiuhe Wang; Kuan Zhang; Wenshuo Zhou; Lei Zhang; Jiang Xu

Researchers reorganized preformed nanoparticles so a metabolic RNA becomes available before the therapeutic payload. This staged architecture increased cellular energy availability and subsequent protein production. Mouse cancer and infectious-disease vaccine experiments showed improved immune activity, supporting spatial organization as an additional delivery design variable. Compatibility across several nucleic acid formats was demonstrated, but human performance remains untested.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1038/s41551-026-01796-3

Reviews & perspectives
Human immunology

Self-amplifying RNA and circular RNA vaccines: mechanisms, delivery strategies, and prospects for long-lasting immunity

Nageen Sardar; Shoaib Manzoor

This review compares self-amplifying and circular RNA vaccine architectures, expression kinetics, delivery approaches, and immune responses. It discusses the different reasons these platforms may extend antigen production or reduce dose requirements, alongside manufacturing, purity, reactogenicity, and regulatory challenges. It is a synthesis of heterogeneous preclinical and early clinical evidence, not a new head-to-head trial establishing superiority over conventional mRNA vaccines.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1016/j.humimm.2026.112083

Original research
Science advances

Targeting tumor-associated macrophages using mRNA lipid nanoparticles for cytotoxic T lymphocyte-mediated cancer immunotherapy

Rui Chen; Letao Xu; Alexander H. Staudacher; Xing Wang; Ruoxuan Jia; John W. Finnie; Xiaoyan Wang; Dawn M. Whelan; Michael P. Brown; Chun-Xia Zhao

Antibody-coated nanoparticles targeted TREM2-expressing tumor-associated macrophages and combined CXCL9-encoding mRNA with a Toll-like receptor agonist. The approach remodeled the tumor immune environment and increased cytotoxic T-cell infiltration and activity. Additional checkpoint blockade strengthened immune responses in experimental models. This is a targeted delivery and combination-immunotherapy proof of concept, rather than evidence of efficacy in patients.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1126/sciadv.aed9568

Original research
Advanced science (Weinheim, Baden-Wurttemberg, Germany)

Dual pKa Lipid Nanoparticles for Lung-tropic mRNA Delivery and pH-Programmed Endosomal Escape

Seong Gi Lim; Minju Lee; Yiming Wang; Eunjin Choi; Ji Sun Park; Kyungmin Park; Hayoung Jeon; Donghyun Kim; Donghyun Lee; Yeeun Lee; Kee‐Pyo Kim; Eunha Kim; Heebeom Koo

The study introduces an ionizable lipid with two apparent ionization transitions that persist after nanoparticle formulation. Following intravenous administration, the particles favored pulmonary mRNA expression and improved outcomes in an experimental acute lung inflammation model. Simulations linked protonation states to membrane interactions. The work provides a mechanistic design hypothesis, with selectivity and tolerability established only in the tested preclinical settings.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1002/advs.77387

Methods
AAPS PharmSciTech

Spray Freeze Drying for Solid Formulations of RNA Lipid Nanoparticles

Kinnari Santosh Arte; Rachana Sapkota; Chanakya D. Patil; Yijing Huang; Eric J. Munson; Sajal Patel; Nicole Payton; Rushit Lodaya; Qi Tony Zhou; Li Lily Qu

Using yeast RNA as a model payload, researchers evaluated atomization, freezing, drying temperature, and annealing during spray-freeze drying of RNA-LNPs. Powder diffraction, microscopy, and solid-state NMR supported characterization. Sucrose outperformed trehalose in the tested systems, and annealing improved stability. Because the payload was model RNA, these findings do not directly establish therapeutic mRNA expression potency or clinical-product stability.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1208/s12249-026-03516-1

Original research
International journal of biological macromolecules

Localized hydrogel delivery of photoactivatable mRNA lipid nanoparticles and hyaluronidase for postoperative TNBC immunotherapy

Ao Hoi Tong; Haichao Zhu; Chenming Zou; Bingshu Liang; Xueer Wu; Shengrong Guo

An injectable hydrogel co-delivered hyaluronidase and light-responsive nanoparticles carrying IL-12 and GM-CSF mRNAs. The design combined stromal remodeling, local retention, and photoactivated intracellular delivery. In a postoperative mouse breast-cancer model, treatment reduced recurrence and altered local and systemic immune responses. The multiple-component system remains experimental, with light access, long-term safety, and clinical feasibility requiring further work.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1016/j.ijbiomac.2026.154367

Original research
Proceedings of the National Academy of Sciences of the United States of America

Intratumoral injection of EpCAM BITE, IL-12, and GM-CSF mRNA-LNPs blocks the growth of local treated and distant untreated tumors

Vita Golubovskaya; Liang Hu; Shiming Zhang; John Sienkiewicz; Hua Zhou; Robert Berahovich; Jinying Sun; Le Li; Walter Bodmer; Lijun Wu

Investigators combined mRNAs encoding an EpCAM-directed T-cell engager, IL-12, and GM-CSF through intratumoral nanoparticle administration. In partially humanized mouse xenograft experiments, the combination altered immune activity in both injected and uninjected tumors and inhibited tumor growth. The study supports localized production of several immune proteins, while the model cannot establish safety or effectiveness across human cancers.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1073/pnas.2616059123

Methods
Analytical Chemistry

Advancing Charge Detection Mass Spectrometry for Characterizing Large, Intact mRNA Constructs

Lohra M. Young; Benjamin E. Draper; Mark Chipley; Lauren F. Barnes; Brian Gau; Andrew Dawdy; Alex Kearns; John Orlet; Thomas W. Powers; Martin F. Jarrold

The study develops charge detection mass spectrometry for intact mRNA constructs spanning 997–4,522 nucleotides. Optimized preparation and calibration enabled length determination with 0.5% uncertainty, comparisons of modified nucleotides and poly(A) tails, and analysis after extraction from lipid nanoparticles. The method adds intact-molecule information, while counterion effects and orthogonal identity and impurity measurements remain relevant.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1021/acs.analchem.6c03854

Original research
Nature Communications

Nontoxic mRNA vehicles based on electrically neutral self-assembling peptides

Zhihao Zhang; Mahnseok Kye; You-jin Jung; Hye-soo Lee; Shouqin Feng; Yong-beom Lim

Electrically neutral self-assembling peptides were developed as mRNA vehicles that form RNA-containing nanotubular assemblies. Experiments examined delivery alongside cytotoxicity and membrane-disruption behavior, reporting favorable readouts in tested systems. This is an alternative peptide carrier rather than an LNP formulation. The peer-reviewed early article supports further development, but its title should not be interpreted as universal or clinical nontoxicity.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1038/s41467-026-77061-7

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