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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

DOI: 10.1021/acs.molpharmaceut.6c00239

Original research
ACS Applied Materials & Interfaces

Stabilizing Anionic mRNA Lipid Nanoparticles by Cleavable Crosslinking of Cholesterol

Yunhe Su; Joseph Choy; Xiang Liu; Yining Zhu; Jinghan Lin; Christine Wei; Kailei D. Goodier; Di Yu; Leonardo Cheng; Milan Patel; Xiaoya Lu; Jingyao Ma; Jialiang Wang; Hai-Quan Mao

Acid-cleavable cholesterol-derived crosslinkers and PEG-diamines stabilized anionic LNPs that otherwise lost activity during purification. By tuning crosslinking architecture, researchers balanced structural integrity with RNA release and improved splenic mRNA expression. Mechanistic analyses implicated intracellular processing as well as release behavior. These formulation-specific animal results do not establish general T-cell targeting or clinical manufacturing readiness.

DOI: 10.1021/acsami.6c06888

Methods
ACS Nano

Nanopore-Mediated Assembly Enables Precise and Continuous Synthesis of mRNA-Encapsulated Lipid Nanoparticles for COVID-19 Vaccines

Zhixiang Liu; William Stewart; Yilong Teng; Yufeng Song; Maoping Tang; Yuxuan Guo; Xue-Qing Zhang; Kamalesh K. Sirkar; Xiaoyang Xu

A hollow-fiber membrane platform uses dense nanopore arrays to control localized mixing during lipid nanoparticle assembly. The continuous process generated tunable particle sizes, narrow distributions, and high encapsulation, with particle properties linked to membrane pore size. Multiple lipid chemistries and nucleic acid payloads were compatible, and cell and animal studies supported activity. Commercial GMP performance remains to be established.

DOI: 10.1021/acsnano.6c00729

Reviews & perspectives
mAbs

Setting expectations for current and future directions of native mass spectrometry in the biopharmaceutical industry

Elizabeth Hecht; Esther Martin; Idlir Liko; Andrew Mahan; Aniruddha Sahasrabuddhe; Nastaran N Tajoddin; Iain D G Campuzano

This industry perspective examines native mass spectrometry as a complement to established biopharmaceutical characterization methods. It discusses intact assemblies, binding, stoichiometry, and heterogeneity, while identifying throughput, sensitivity, automation, and access limitations. The authors emphasize integration with analytical workflows rather than universal replacement of existing methods.

DOI: 10.1080/19420862.2026.2699078

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