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Research Literature

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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
Nature Materials

An inherent T cell-activating mRNA delivery carrier for in vivo CAR T generation

Qiannan Cao; Yingli Yao; Wenming Zheng; Hongqian Liu; Mingxia Jiang; Dayang Xie; Siting Zhang; Pijun Su; Huilin Yuan; Xiaoyuan Chen; Huapan Fang; Huayu Tian

A polymer-lipid carrier incorporating arginine-modified oligoethylenimine combined T-cell activation with mRNA delivery without an added targeting ligand. The formulation favored splenic delivery and engaged PI3K-AKT-mTOR signaling. FAP-CAR mRNA generated functional CAR T cells in experimental cancer and fibrosis settings. These are preclinical results; the article also has a subsequent publisher correction that should accompany interpretation.

In Vivo Cell Engineering & Gene EditingmRNA / LNP
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DOI: 10.1038/s41563-026-02675-7

Original research
ACS Biomaterials Science & Engineering

Mannosylated Spleen-Targeted Lipid Nanoparticles Enable Enhanced mRNA Delivery to Antigen-Presenting Cells

Shu Zhang; Yaxi Li; Aygun Teymur; Bowen Yang; Sheereen Majd; Chandra Mohan; Tianfu Wu

A mannose-containing fifth lipid was incorporated into spleen-targeted LNPs to combine endogenous organ enrichment with receptor-associated uptake. Adjusting mannose-lipid content shifted distribution toward the spleen and improved macrophage transfection. Experiments identified uptake by macrophages and conventional dendritic cells, alongside freeze-thaw stability testing. These findings support immune-delivery development, while therapeutic and human targeting performance remain undetermined.

mRNA / LNP
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DOI: 10.1021/acsbiomaterials.6c00494

Original research
Nature Biomedical Engineering

Engineered lipid nanoparticles for in vivo and durable editing of haematopoietic stem cells within humanized mice

Jingjing Du; Zijin Luo; Dan Xie; Yan Chen; Ming Yang; Qiang Li; Lisha Wang; Lu Han; Yiming Zhang; Haiwei Li; Zilin Lan; Haoping Shi; Yinghui Li; Qiang Cheng; Fang Dong; Yingdai Gao; Yao Yao; Tao Cheng; Tuo Wei; Shuquan Rao

Anti-CD34-conjugated LNPs delivered reporter mRNA and gene-editing cargos to human hematopoietic stem and progenitor cells. Intrafemoral administration in humanized mice supported durable BCL11A-enhancer editing and fetal hemoglobin reactivation; ELANE editing partially restored neutrophil development in another model. The study addresses difficult stem-cell targeting but uses a specialized administration route and preclinical systems.

mRNA / LNP
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DOI: 10.1038/s41551-026-01765-w

Reviews & perspectives
Physchem

Quantifying Lipid Components in Messenger RNA–Lipid Nanoparticle Formulations: A Review of Liquid Chromatography–Mass Spectrometry Methods

Manohar Aele; Naveen Madamsetti; Vikram Godishala; Swati Dahariya; Aditya Velidandi

This review compares liquid chromatography and mass spectrometry strategies for quantifying ionizable lipids, PEG lipids, helper phospholipids, cholesterol, and degradation products in mRNA-LNP formulations. It considers sensitivity, linearity, run time, matrix effects, and stability-indicating measurements. The comparison supports method selection rather than demonstrating a single validated release assay applicable to every formulation.

mRNA / LNP
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DOI: 10.3390/physchem6030049

Original research
ACS Nano

Intratracheal Delivery of mRNA Lipid Nanoparticles Reprograms Alveolar Macrophages for Pulmonary Cancer Immunotherapy

Jiayi Zhou; Tanzhuoyi Li; Weiwei Zhang; Panshuang Qiao; Huiyu Zhang; Zihan Ding; Yilei Lu; Jiongran Yu; Jing Ding; Hang Chen; Dezhong Ji; Yiguang Wang; Binlong Chen

Comparing intranasal and intratracheal vaccination, researchers found that total lung expression alone poorly predicted functional delivery to alveolar macrophages. Intratracheal mRNA-LNP delivery produced stronger macrophage transfection and antigen presentation, with improved tumor control in pulmonary models. Depleting alveolar macrophages eliminated protection, supporting their mechanistic role. These administration and efficacy findings remain preclinical.

mRNA / LNP
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DOI: 10.1021/acsnano.6c04529

Methods
RNA

Efficient production of a self-amplifying RNA vaccine sequence with the single subunit RNA polymerase from Klebsiella phage 32 utilizing the native AU initiating dinucleotide

Marcus A. Price; Maryia Trubitsyna; Jane E. Paget; Benjamin W. Baker; Frances Turner; Susan J. Rosser

Researchers identified Klebsiella phage 32 RNA polymerase as an alternative to T7 for RNA production. The enzyme tolerated a broad range of temperatures, pH values, and salt conditions. For an 11,551-nucleotide self-amplifying RNA retaining its native AU initiation, production was 9.3-fold higher than the T7 comparison. These laboratory results do not establish GMP-scale performance.

mRNA / LNP
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DOI: 10.1261/rna.081020.126

Original research
Molecular Therapy

Capless self-amplifying mRNA vaccine induces dose-sparing protective immunity against HPAI clade 2.3.4.4 H5 virus in mice

Beom Kyu Kim; Ji-Hyun Park; Won-Suk Choi; Sol Oh; Se Hee An; Gi Chan Lee; Santosh Chokkakula; Chang-Ung Kim; Ju Hwan Jeong; Seong Cheol Min; Dong Gyu Lee; Ju Ryeong Lee; Sun-Woo Yoon; Doo-Jin Kim; Timothy J. Mahony; Richard J. Webby; Young Ki Choi; Yun Hee Baek; Min-Suk Song

A Coxsackievirus B5 replicon used internal ribosome entry site-driven translation to generate a capless self-amplifying RNA vaccine. Genetic optimization improved expression, and LNP-formulated H5 antigen constructs induced neutralizing antibodies and cellular responses in mice. Low-dose vaccination protected against lethal H5N8 challenge. The platform changes capping requirements, but human immunogenicity, manufacturing performance, and safety remain unestablished.

mRNA / LNP
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DOI: 10.1016/j.ymthe.2026.07.047

Methods
Bioconjugate Chemistry

RNA Size and Structure Modulate the Apparent p K a of Ionizable Lipid Nanoparticles

Anastasiia Priss; Olha Lytvynenko; Vaclav Vanek; Frantisek Sedlak; Klara Grantz Saskova; Petr Cigler

Across six ionizable lipids, researchers encapsulated RNAs ranging from short oligonucleotides to 4.5-kilobase mRNA and measured apparent pKa using a fluorescence assay. Both RNA length and structure altered particle ionization, with lipid-dependent shifts. The study indicates that cargo is an active formulation variable; it does not directly establish changes in therapeutic efficacy or organ targeting.

mRNA / LNP
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DOI: 10.1021/acs.bioconjchem.6c00177

Reviews & perspectives
Journal of Biomedical Science

The current landscape of mRNA therapy and the strategies for mRNA purification and dsRNA removal

Jin-He Liu; Jian Zang; Jing-Ru Xu; Xue-Bin Ran; Min Su; Wang-Ming Zhang; Zhang-Wen Ge; Qiao-Yang Sun; Ling-Wen Ding

This review examines mRNA therapy and impurity control during in vitro transcription, focusing on purification strategies and double-stranded RNA removal. It compares detection and separation approaches with attention to RNA integrity, recovery, and manufacturing feasibility. Construct-specific differences and analytical limitations complicate direct comparisons; the review does not establish a universal acceptable dsRNA limit for every product.

mRNA / LNP
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DOI: 10.1186/s12929-026-01277-4

Original research
ACS Nano

Decoding the Functional Roles of Individual Components in mRNA Lipid Nanoparticles

Kexin Su; Zichuan Wang; Lu Shi; Xudong Fu; Xin Sheng; Na Kong; Tengfei Xu; Shuai Liu

Researchers removed individual components from mRNA-LNP formulations to distinguish the contributions of ionizable lipid, cholesterol, phospholipid, and PEG-lipid. Animal experiments linked these components differently to liver delivery, extrahepatic expression, particle size, and inflammation. The results challenge uniform assumptions about helper-lipid functions, while remaining dependent on the specific formulations and experimental systems tested in this study.

mRNA / LNP
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DOI: 10.1021/acsnano.6c07039

Original research
Advanced Science

Molecular Dynamics‐Guided Sterol Engineering of mRNA‐Lipid Nanoparticles Reprograms Biodistribution and Enhances Spleen‐Selective Immunity

Sanghyuk Jeon; Seo‐Hyeon Bae; Jungyong Ji; Jisun Lee; Hosam Choi; Min‐Ho Kang; Sang‐In Park; Hyemin Kim; Nakyung Lee; Hajin Lee; Seonghoon Kim; Jungmin Kim; Subin Yoon; Seonghyun Lee; Seongje Cho; Dahyeon Ha; Ayoung Oh; Sohee Jo; Huijeong Choi; Yeeun Lee; Sowon Lee; Hyo‐Jung Park; Gitak Nam; Jisu Shin; Yujin Kang; Wonpil Im; Kiyoun Lee; Jae‐Hwan Nam

Nine bile-acid-derived sterols varied hydroxylation and alkyl-tail chemistry to probe LNP organization and organ expression. Molecular simulations and experiments linked membrane descriptors with encapsulation and formulation behavior. Replacing cholesterol shifted expression toward the spleen, and a lead sterol enhanced antigen-specific responses. The work offers a preclinical formulation framework rather than validated prediction of human biodistribution.

mRNA / LNP
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DOI: 10.1002/advs.76671

Original research
Molecular Pharmaceutics

Targeted mRNA Delivery Using Bispecific Antibody-Lipid Nanoparticle Complexes

James Collin Hickey; Tracoyia Roach; Britteny Cassaidy; Rudolf Hergesheimer; Noah Franklin; Jeffrey Morin; Sarah Wagman; Justin Cohen; David Morrissey; Javier Chaparro-Riggers; Patrick Lim Soo

Bispecific antibodies were used to bridge PEG motifs on LNPs and selected cellular surface markers without elaborate chemical conjugation. The platform enabled targeted mRNA delivery in cell models and transferrin-receptor-associated delivery in vivo. Researchers also measured endosomal responses at different antibody-loading ratios. Splenic enrichment supports further immune-cell targeting studies, but does not establish a clinical delivery solution.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1021/acs.molpharmaceut.6c00239

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