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.
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.
Why it is included: Broadens the carrier landscape beyond lipids; long-term tolerability, biodistribution, and therapeutic performance require further preclinical and clinical investigation.
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.
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.
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.
Why it is included: Helps connect discovery formulations with development requirements; particle size and encapsulation alone cannot establish a complete manufacturing control or comparability strategy.
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 Nano Letters · DOI 10.1021/acs.nanolett.6c01762
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.
Why it is included: Explains an important in vitro–in vivo translation gap; pregnancy applications require rigorous maternal, fetal, and immunological safety assessment.
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.
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.
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.
