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.
Hassoun H; Pascarel C; Erny A; Giang E; Garapon C; Gerossier L; Coiffier C; Monge C; Verrier B; Archer F; Aznar N International journal of pharmaceutics · DOI 10.1016/j.ijpharm.2026.127550
Researchers screened PEG-free hybrid particles containing a polylactic acid core and engineered lipid surface. A lead formulation preserved particle size and reporter activity after vibrating-mesh nebulization, outperforming the tested SM-102 reference under those conditions. Non-nebulized particles also transfected organoids and primary airway cultures. The authors identify mucus transport, aerosol deposition, and in vivo efficacy as unresolved next steps.
Why it is included: Offers a PEG-free architecture resistant to the tested nebulization process; advanced in vitro models do not establish effective pulmonary dosing in vivo.
Stephen J. Kent; Shiyao Li; Thakshila H. Amarasena; Arnold Reynaldi; Michael G. Leeming; Jennifer A. Juno; Adam K. Wheatley; Georgia Deliyannis; Dale I. Godfrey; Terry Nolan; Colin W. Pouton; Miles P. Davenport; Yi Ju ACS Nano · DOI 10.1021/acsnano.6c09226
Serial blood samples from 73 vaccine recipients were analyzed using ddPCR for total and long-range-linked mRNA and LC-MS for ionizable lipids. RNA and lipid decay differed across three vaccine platforms. Cohorts differed in dose, vaccination history, and sampling schedules. Detecting circulating RNA fragments does not by itself establish continued protein expression, clinical toxicity, or comparative vaccine effectiveness.
Why it is included: Provides human benchmarking for RNA and lipid measurements while distinguishing total fragments, intact transcripts, functional exposure, and clinical outcomes.
Mariah L. Arral; Namit Chaudhary; Katherine C. Fein; Alexandra N. Newby; Saigopalakrishna S. Yerneni; Jilian R. Melamed; Samuel T. LoPresti; Daria M. Strelkova Petersen; Kathryn A. Whitehead Drug delivery and translational research · DOI 10.1007/s13346-026-02225-3
This repeat-dosing study examined whether changes in PEG chemistry, PEG concentration, RNA cargo, or administration route could overcome efficacy loss after an immunogenic nanoparticle dose. None reliably restored delivery in the tested setting, and reduced activity tracked anti-PEG antibodies. The results emphasize the interaction between ionizable lipids and innate immunity, without establishing that every PEG-containing product will behave identically.
Why it is included: Highlights repeat-dose immunogenicity as a platform design constraint; the tested formulations cannot establish a universal clinical response to PEGylated nanoparticles.
Researchers combined a 520-member degradable lipid library with interpretable machine learning and a 10,920-member virtual design space. Independent mouse experiments identified PA97MD101 as a lead for hepatic mRNA expression, Cre-mediated recombination, and Cas9-based TTR suppression. The study links screening predictions with functional animal validation, without establishing clinical safety or efficacy.
Why it is included: Combining interpretable models with independent animal testing may improve lipid selection beyond cell-based screens and guide more efficient formulation discovery.
Yue Ma; Yaoxian Han; Jiawei Zhou; Yuxin Xiao; Jie Liu; Wenjie Sun; Hui Yang; Guangyu Hu; Shangang Li; Weizhi Ji; Wenting Guo; Lei Zhang; Yongchang Chen Science China. Life sciences · DOI 10.1007/s11427-025-3541-0
A design-of-experiments approach produced an SM-102-derived formulation with less hepatic reporter expression and preserved or improved expression after local administration. Experiments included intramuscular, intracerebroventricular, and intravitreal routes. Mechanistic analyses associated the change with altered protein binding, systemic exposure, and hepatocyte trafficking. These route-specific results support formulation optimization but do not demonstrate noninvasive access to the brain or eye.
Why it is included: Provides a practical strategy to reduce hepatic spillover from local dosing; expression and tolerability findings remain dependent on route and preclinical models.
Adam Cook; Pavan K. Yadav; Ekram W. Helmy; Kseniia Vlasova; Howard Y. Chang; Paul A. Wender Journal of the American Chemical Society · DOI 10.1021/jacs.6c14175
A study designed ionizable lipids specifically for circular RNA, whose topology differs from linear mRNA. Lead lipid iL-19 combined aminoethoxy head groups with doubly branched tails and improved protein expression after intramuscular delivery in mice relative to several benchmark lipids. The results establish preclinical design principles, not clinical superiority.
Why it is included: Circular RNA programs may benefit from dedicated lipid optimization instead of assuming formulations developed for linear RNA will transfer unchanged.
Chun K; Choi SY; An K; Jo DH; Lee H Journal of controlled release : official journal of the Controlled Release Society · DOI 10.1016/j.jconrel.2026.115453
A C12-200-based formulation was optimized for movement and cellular delivery in the protein-poor vitreous environment. It co-delivered RB1 mRNA and triptolide, improving antiproliferative activity and suppressing tumors in an orthotopic retinoblastoma model after intravitreal administration. Retinal evaluations supported tolerability during the study period. The combination remains preclinical and requires longer ocular safety assessment and pediatric translation studies.
Why it is included: Demonstrates tissue-environment-specific engineering for ocular combination therapy; animal tumor suppression and short-term retinal assessments do not establish pediatric clinical safety.
Ciacci Zanella G; Vincent ML; Flores L; Aljets EK; Paiva RC; Markin A; Inderski B; Dwivedi G; Weissman D; Wymore Brand M; Santos JJS; Hensley SE; Anderson TK; Gauger PC; Baker AL Journal of virology · DOI 10.1128/jvi.00848-26
Researchers selected eight hemagglutinin sequences to represent circulating swine influenza diversity and evaluated individual and multivalent mRNA vaccines in pigs. The multivalent formulation elicited responses against its component antigens and protected against lung lesions after the tested challenge. This large-animal veterinary study supports adaptable multivalent design, while protection across untested strains and direct relevance to human influenza remain unresolved.
Why it is included: Adds large-animal evidence for multivalent RNA vaccination; the challenge design does not establish universal strain coverage or human protection.
Circular RNA nanoparticles encoding the malaria transmission antigen Pvs25 were compared with a modified linear mRNA vaccine in mice. Both platforms induced antigen-specific responses, and booster immunization generated antibodies that blocked parasite development in mosquito assays. The findings support further evaluation of circular RNA for transmission-blocking vaccination, without establishing greater efficacy, durability, or manufacturing economy than linear mRNA in humans.
Why it is included: Extends circular RNA vaccine evidence beyond common viral targets; mouse immunogenicity and mosquito assays require confirmation in larger animals and humans.
Haixia Gao; Yuan Fang; Zhidan Tian; Chuanxin Guo; Pei Wang; Tao Liu; Yan Sun; Pingjing Zhang; Qijun Qian iScience · DOI 10.1016/j.isci.2026.117390
Screening eight ionizable lipids identified a lead formulation that delivered reporter RNA to several immune-cell types. Researchers then used it to engineer primary human T cells expressing a MUC1-directed CAR, with cytotoxic activity against antigen-positive tumor cells in vitro. Animal reporter experiments supported delivery feasibility, but the study does not demonstrate therapeutic CAR-T generation inside patients or animals.
Why it is included: Supports transient, nonviral T-cell engineering; in vitro MUC1-directed killing does not establish in vivo CAR-T therapeutic efficacy or clinical manufacturing readiness.
Kyle J. Tynan; Karndeep Singh; Trina Mouchahoir; Mark S. Lowenthal; Karen W. Phinney Discover Pharmaceutical Sciences · DOI 10.1007/s44395-026-00058-0
This review evaluates electrophoresis, chromatography, sequencing, and mass spectrometry for measuring mRNA drug-substance identity, length, concentration, intactness, and purity. It compares throughput, sample preparation, and total analysis time while considering multi-attribute methods used for protein therapeutics. The authors identify opportunities for integrated mRNA analytics, rather than validating a universal platform that replaces all individual quality assays.
Why it is included: Provides a framework for reducing analytical burden while requiring explicit evidence of which quality attributes are measured and which risks remain uncovered.
Jinbi Tian; Khanh T. M. Tran; Brett H. Pogostin; Olivia Sheridan; Sevinj Mursalova; Amy H. Lee; Shuai Liu; Jaya Hamkins; Daniel Antov; Alana L. Power; Zane S. Dash; Dongsoo Yun; Mina Konaković Luković; Robert S. Langer; Ana Jaklenec Nature Biotechnology · DOI 10.1038/s41587-026-03331-w
The AGENT platform combines Bayesian optimization with high-throughput experiments to identify thermostable mRNA-LNP formulations through six iterations in approximately one month. Solid-state model formulations based on SM-102 and ALC-0315 retained biological activity after more than two months at 37°C. Animal immunogenicity supported further development, but these formulation-specific findings do not eliminate cold-chain requirements for mRNA products generally.
Why it is included: Illustrates efficient formulation optimization for thermostability; real products require long-term potency, transport, reconstitution, and safety data under their intended conditions.
