Explore recent mRNA, saRNA, circular RNA, and LNP research on delivery, therapeutic translation, safety, analytical characterization, and manufacturing.
Selected for substantive contributions to delivery, translation, analytics, manufacturing, and safety. Original publication dates and evidence levels are retained. This library covers the latest 120 days; individual published guides remain available.
Kai Jiang; Bing Shao; Runjie Li; Tianzhu Liang; Chengying You; Lili Wang; Jie Cen; Jiajia Tan; Yanhao Zhang; Minglong Chen; Shiyong Liu Angewandte Chemie International Edition · DOI 10.1002/anie.3823572
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.
Why it is included: Supports hydrophobic-domain engineering for APC-centered vaccination; model-antigen prophylactic protection does not establish efficacy against established patient tumors.
Shu Zhang; Yaxi Li; Aygun Teymur; Bowen Yang; Sheereen Majd; Chandra Mohan; Tianfu Wu ACS Biomaterials Science & Engineering · DOI 10.1021/acsbiomaterials.6c00494
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.
Why it is included: Combines ligand targeting and organ-selective formulation in one platform; uptake enrichment alone does not establish clinical immunotherapy efficacy.
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 Nature Biomedical Engineering · DOI 10.1038/s41551-026-01765-w
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.
Why it is included: Advances extrahepatic delivery to long-lived human stem cells; intrafemoral mouse experiments do not establish routine systemic treatment feasibility.
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.
Why it is included: Connects lipid composition with degradation monitoring; developers must establish formulation-specific suitability, recovery, and validation rather than relying on a generic lipid assay.
Marcus A. Price; Maryia Trubitsyna; Jane E. Paget; Benjamin W. Baker; Frances Turner; Susan J. Rosser RNA · DOI 10.1261/rna.081020.126
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.
Why it is included: Highlights transcription options for long saRNA constructs; scale-up requires evaluating impurity profiles, capping compatibility, process robustness, and batch consistency.
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.
Why it is included: Demonstrates that administration route and cell-level expression can outweigh bulk organ signals; human pulmonary tolerability and efficacy remain untested.
Anastasiia Priss; Olha Lytvynenko; Vaclav Vanek; Frantisek Sedlak; Klara Grantz Saskova; Petr Cigler Bioconjugate Chemistry · DOI 10.1021/acs.bioconjchem.6c00177
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.
Why it is included: Warns against transferring pKa assumptions between RNA cargos; apparent-pKa shifts require biological validation before inferring delivery or safety changes.
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 Molecular Therapy · DOI 10.1016/j.ymthe.2026.07.047
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.
Why it is included: Introduces a cap-independent saRNA architecture with mouse dose-sparing evidence; clinical dosing and process advantages have not yet been demonstrated.
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 Journal of Biomedical Science · DOI 10.1186/s12929-026-01277-4
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.
Why it is included: Useful for selecting purification and impurity assays; product specifications still require validated measurement capabilities and evidence linking impurities to biological risk.
Kexin Su; Zichuan Wang; Lu Shi; Xudong Fu; Xin Sheng; Na Kong; Tengfei Xu; Shuai Liu ACS Nano · DOI 10.1021/acsnano.6c07039
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.
Why it is included: Makes helper-lipid choice a mechanistic design variable; component-removal results should not be generalized to every lipid chemistry or dose.
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.
Why it is included: Highlights sterols as an independent delivery-design axis; simulation correlations and acute animal tolerability do not establish long-term clinical safety.
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 Molecular Pharmaceutics · DOI 10.1021/acs.molpharmaceut.6c00239
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.
Why it is included: Provides a modular targeting workflow for immune-cell delivery studies; receptor expression, antibody loading, and in vivo translation remain critical limitations.
