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.
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.
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.
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.
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.
Seo‐Hyeon Bae; Jisun Lee; Jae‐Hun Ahn; Hosam Choi; Huijeong Choi; Jungmin Kim; Minho Kang; Ho Rim Oh; So Hyun Park; Eun Young Oh; Sanghyuk Jeon; Yeeun Lee; Yu‐Sun Lee; Na‐Young Lee; Hee‐Jin Bae; Jina Kwak; Jooil Kim; Nakyung Lee; Beomsun Kang; Ji‐Hye Kim; Eunsaem Song; Daesub Song; Hyunho Yoon; Sang‐Myeong Lee; Hyewon Youn; Kiyoun Lee; Byeong‐Cheol Kang; Jae‐Hwan Nam Advanced Science · DOI 10.1002/advs.76539
A library of 56 ionizable lipids combined biodegradable disulfide linkages with different hydrophobic tail lengths and branching patterns. Structure-activity testing linked tail architecture to endosomal escape, translation, and biocompatibility. Optimized particles reduced cytotoxicity and cytokine induction, with immune-response evaluation extending to a nonhuman primate model. These findings support lipid design, rather than establishing human safety.
Why it is included: Offers experimentally grounded tail-chemistry design rules and primate evidence; reduced inflammatory readouts do not guarantee clinical safety.
