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mRNA / LNP 67

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

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Original research
ACS nano

Targeted Gastrointestinal Delivery of mRNA Lipid Nanoparticles Enables Systemic Vaccination and Glucagon-like Peptide-1 Metabolic Therapy

Abdulraouf M. Abbas; Ramy Ghanim; Sebastian Rudden; David Schultz; Bora Jang; Avraham Shakked; Hyejin Kim; James E. Dahlman; Alex Abramson

Investigators administered nanoparticles to several gastrointestinal submucosal sites to examine route-dependent targeting. Gastric delivery increased pancreatic exposure in rodents, while GLP-1 mRNA improved glucose regulation in mice. Buccal administration supported local and lymphatic targeting with vaccine responses. These are tissue-directed administration experiments; they do not establish that conventional swallowed nanoparticles can survive digestion and reproduce the same delivery profile.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1021/acsnano.5c18549

Original research
Nature biotechnology

Lipid nanoparticles optimized for large RNA cargo and tissue targeting enhance in vivo genome editing

Songtao Dong; Fanglin Gong; Tyler Thomson; Yunshu Cai; Lauren Healy; Rick X. Z. Lu; Ziyu Zhou; Yue Xu; Jingan Chen; Margarita Savguira; Xianglei Fu; Sijin Luozhong; Muye Zhou; Payton Kirtley; Brandon K. Wilder; Bowen Li

A lipid screen explicitly incorporated a large base-editor transcript rather than relying on small reporter RNA. The lead lipid retained favorable RNA interactions and membrane-disrupting structure as cargo size increased. It improved editing in liver, brain, and lung using different administration routes, including intrathecal and intratracheal dosing. The findings do not establish systemic delivery to all three organs.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1038/s41587-026-03298-8

Methods
Nature Biotechnology

Accelerated discovery of thermostable mRNA–lipid nanoparticle vaccines using data-efficient AI

Jinbi Tian; Khanh T. M. Tran; Brett H. Pogostin; Olivia Sheridan; Sevinj Mursalova; Amy H. Lee; Shuai Liu; Jaya Hamkins; Daniel Antov; Alana L. Power; Zane S. Dash; Dongsoo Yun; Mina Konaković Luković; Robert S. Langer; Ana Jaklenec

The AGENT platform combines Bayesian optimization with high-throughput experiments to identify thermostable mRNA-LNP formulations through six iterations in approximately one month. Solid-state model formulations based on SM-102 and ALC-0315 retained biological activity after more than two months at 37°C. Animal immunogenicity supported further development, but these formulation-specific findings do not eliminate cold-chain requirements for mRNA products generally.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1038/s41587-026-03331-w

Methods
Advanced Materials

Increasing Lipid Nanoparticle mRNA Copy Number Improves Transfection Potency

Yao Zhang; Jerry Leung; Judy Cheng; Arash Momeni; Albert Kamanzi; Ariadne Tuckmantel Bido; Suiyang Liao; Emma Kang; Colton Strong; Christian J. Kastrup; Sabrina Leslie; Miffy Hok Yan Cheng; Pieter R. Cullis

Researchers modified buffer exchange into a two-step dialysis process, first promoting fusion under acidic, higher-ionic-strength conditions while retaining ethanol, then removing ethanol and raising pH. Compared with one-step exchange, the process increased mRNA copies per particle, reduced empty particles, and improved transfection in cells and animals. These formulation-specific results do not establish that removing empties always improves every product.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1002/adma.75174

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

Immune Checkpoint Inhibitor as a Fifth Component of Lipid Nanoparticles Enables Lymph Node-Targeting and Augments mRNA Vaccine Efficacy

Ha M; Kim J; Kim S; Naidu GS; Cho S; Yong SB

Researchers incorporated an amphiphilic PD-L1 inhibitor as an additional nanoparticle component rather than administering it separately. The modified formulation increased lymph-node reporter expression and strengthened vaccine-associated immune responses in experimental models. Similar targeting effects were observed with two ionizable lipid backbones. These results suggest formulation-dependent immune targeting, without proving broad applicability or clinical benefit across tumor types.

mRNA / LNP
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DOI: 10.1002/advs.77923

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

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
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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
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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

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