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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
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
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DOI: 10.1038/s41467-026-77061-7

Methods
Journal of the American Chemical Society

Photochemistry-Based Development of Ionizable Lipid Library for mRNA-Lipid Nanoparticle Delivery In Vivo

Simin Chun; Hyorim Nam; Donghyun Lee; Yeeun Lee; Cheol Hui Park; Chaehwan Lim; Donghyun Kim; Ji Sun Park; Kee-Pyo Kim; Hak Soo Choi; Heebeom Koo

Visible-light-driven multicomponent synthesis generated 275 branched amine-containing ionizable lipids from modular building blocks. The platform linked one-pot synthesis with purification-free cell screening and subsequent animal evaluation. A lead lipid improved expression relative to the tested MC3 formulation, and formulation adjustment enabled organ-selective delivery. The work accelerates discovery but does not establish a clinically optimized or validated manufacturing process.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1021/jacs.6c13674

Original research
Cell Biomaterials

A branched ionizable lipid nanoparticle platform for versatile in vivo delivery of nucleic acids: Validation from mRNA to capped circular RNA

Seigo Kimura; Susumu Tsutsumi; Naoto Nakamura; Shigetomo Tsujihata; Lyu Fangjie; Yuko Nakashima; Shunsuke Kita; Katsumi Maenaka; Fumitaka Hashiya; Masahito Inagaki; Naoko Abe; Yasuaki Kimura; Hiroshi Abe

The branched ionizable lipid FL0445 supported delivery of linear mRNA and capped circular RNA through a cholesterol-dependent cellular-entry pathway. In obese mice, GLP-1-encoding capped circular RNA produced sustained expression and improved glucose tolerance relative to tested formulations. Inflammatory transcriptional signals were also assessed. The results provide a preclinical delivery proof of concept, not evidence of clinical metabolic efficacy.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1016/j.celbio.2026.100555

Original research
ACS Nano

2-arm-PEG-Oligocations Transiently Shield the Liver Sinusoids to Mitigate Off-Target Hepatic Expression of mRNA Lipid Nanoparticles

Anjaneyulu Dirisala; Bhaskar Chatterjee; Nguyen Bui Thao Le; Kazuko Toh; Miki Matsui-Masai; Saed Abbasi; Xueying Liu; Theofilus A. Tockary; Nan Qiao; Junichi Ishikawa; Jumpei Norimatsu; Yuki Mochida; Shigeto Fukushima; Makoto Oba; Kazunori Kataoka; Satoshi Uchida

Researchers used two-armed PEG conjugated to oligocations to transiently coat liver sinusoidal endothelium before mRNA-LNP exposure. The approach modifies the host delivery barrier rather than the LNP itself, aiming to reduce hepatic entry and off-target expression. Mouse experiments examined reversible coating and clearance. Translation would require evaluating the combined regimen, vascular effects, and repeat-dose safety.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1021/acsnano.6c08403

Original research
Proceedings of the National Academy of Sciences

Overcoming the blood–brain barrier using central nervous system–accessing lipid nanoparticles for enhanced mRNA therapeutics

Siyu Wang; Yichen Zhong; Chang Wang; Meng Tian; Jeffrey L. Bennett; Eliza Bliss-Moreau; Yonger Xue; Changyue Yu; Xucheng Hou; Ya Ying Zheng; Haoyuan Li; Zhengwei Liu; Dinglingge Cao; Diana D. Kang; Binbin Deng; Yizhou Dong

The CA2d ionizable-LNP platform delivered mRNA to brain cells after intravenous administration in mice and nonhuman primates. Reported target populations included neurons, microglia, and astrocytes. In a rat ischemic-stroke model, combined thrombolytic and neuroprotective mRNA cargos reduced injury and improved functional measures. The work expands preclinical CNS delivery evidence without demonstrating human brain delivery or treatment efficacy.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1073/pnas.2538147123

Original research
Nano Letters

Enhancing Lipid Nanoparticle-Mediated Circular RNA and mRNA Expression in the Placenta through Inhibition of IFNAR-JAK-STAT Signaling

Hannah C. Safford; Hannah C. Geisler; Ajay S. Thatte; Kuo-Chieh Liao; Alexandre Poirier; Marshall Padilla; Hannah M. Yamagata; Anushka Agrawal; Amanda M. Murray; Alex G. Hamilton; Kelsey L. Swingle; Emily Fitzgerald; Ori Chalom; Yue Wan; Michael J. Mitchell

Placenta-tropic LNPs produced strong circular-RNA expression in cultured trophoblasts but weaker translation in pregnant mice than linear mRNA. Researchers identified innate immune signaling as a constraint and increased placental expression by inhibiting IFNAR-JAK-STAT pathways. VEGF-encoding cargos provided a therapeutic-payload demonstration. Immune suppression during pregnancy raises separate safety questions that expression improvements alone cannot resolve.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1021/acs.nanolett.6c01762

Methods
Nature Communications

pH-Sensitive Amino Lipid-Driven Pore Formation Enables Endosomal Escape of Lipid Nanoparticles

Akhil Pratap Singh; Kana Shibata; Yusuke Miyazaki; Wataru Shinoda

Molecular simulations examined how ionizable lipid nanoparticles interact with endosomal membranes and release nucleic acids. The authors identified several fusion routes, with a stalk-pore pathway predominating, and linked release to protonation, lipid geometry, membrane tension, and cargo organization. The simplified nucleic acid model used short double-stranded DNA, so findings require validation with therapeutic-length RNA.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1038/s41467-026-76810-y

Reviews & perspectives
Discover Nano

Critical chemistry manufacturing and controls considerations for mRNA lipid nanoparticle translation

Lanbo Liu; Yan Wang; Hua Gao; Jinghui Ruan; Wenna Lu; Tianzhu Liu; Xun Li; Guo-Qiang Zhang; Yating Xiao

This CMC review connects lipid chemistry and manufacturing parameters with critical quality attributes in mRNA-LNP development. It compares microfluidic scale-out with impinging-jet scale-up and emphasizes orthogonal analytics, stability in plasma or serum, lipid impurities, and RNA–lipid adducts. Early comparability planning is recommended. The framework does not demonstrate that one carrier or manufacturing platform is universally superior.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1186/s11671-026-04864-4

Original research
Angewandte Chemie International Edition

Retinoic‐Acid‐Derived Ionizable Lipids Enable Spleen‐Selective Antigen Expression for mRNA Cancer Vaccination

Kai Jiang; Bing Shao; Runjie Li; Tianzhu Liang; Chengying You; Lili Wang; Jie Cen; Jiajia Tan; Yanhao Zhang; Minglong Chen; Shiyong Liu

A 40-member retinoic-acid-derived ionizable-lipid library yielded AT4-13CRA particles with preferential functional expression in splenic antigen-presenting cells. Researchers linked delivery to altered protein coronas and reduced lysosomal retention. An ovalbumin vaccination model showed stronger antigen-specific immunity and prophylactic tumor protection. The artificial antigen and challenge setting limit direct extrapolation to established human cancers.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1002/anie.3823572

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