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.
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 Journal of the American
Chemical Society · DOI 10.1021/jacs.6c13674
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.
Why it is included: Expands lipid chemical diversity with a practical screening workflow; lead superiority is comparator-dependent and requires further translational development.
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.
Why it is included: Links circular-RNA architecture with carrier selection and duration; mouse metabolic effects do not establish human dosing, safety, or therapeutic benefit.
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.
Why it is included: Explores host-barrier modulation as a complement to particle engineering; clinical safety cannot be inferred from transient mouse liver shielding.
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 Proceedings of the National Academy of Sciences · DOI 10.1073/pnas.2538147123
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.
Why it is included: Adds nonhuman-primate evidence for systemic CNS RNA delivery; species differences and neurological safety remain major translational questions.
Akhil Pratap Singh; Kana Shibata; Yusuke Miyazaki; Wataru Shinoda Nature Communications · DOI 10.1038/s41467-026-76810-y
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.
Why it is included: Provides mechanistic design hypotheses for endosomal escape; simplified simulations are not direct evidence of improved therapeutic mRNA delivery.
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.
Why it is included: Connects carrier biology to in vivo CAR-T generation; durable benefit, repeat-dose safety, and applicability to human T cells remain unresolved.
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.
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.
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.
