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.
Meng Tian; Leiming Wang; Zhengwei Liu; Dinglingge Cao; Changyue Yu; Jeffrey L. Bennett; Eliza Bliss-Moreau; Chang Wang; Diana D. Kang; Yonger Xue; Yichen Zhong; Siyu Wang; Haoyuan Li; Xucheng Hou; Binbin Deng; Yizhou Dong Nature Nanotechnology · DOI 10.1038/s41565-026-02326-7
Researchers used the properties of more than 100 central nervous system drugs to design brain-directed ionizable lipids. HX1 nanoparticles delivered RNA and enabled gene editing in mouse brains, delivered reporter mRNA in a nonhuman primate, and reduced radiation-related brain injury in mice carrying Il10 mRNA. These are preclinical findings.
Why it is included: Brain delivery could expand RNA medicine beyond established targets, but repeat-dose safety and human translation still need validation.
Dongmin Xun; Lanqing Li; Jie Zou; Yi Liu; Ziyue Yang; Qianyi Liang; Ke Li; Zhu Zhu; Jicong Zhang; Lijun Lang; Kun Liu; Xinyu Wang; Meilin Tian; Guangyong Chen; Jun Yang; Bolin An; Pheng Ann Heng; Chao Zhong Nature Communications · DOI 10.1038/s41467-026-79039-x
The DeepDelivery platform screened the human proteome for proteins that could serve as mRNA delivery scaffolds. Twelve of 15 experimentally tested candidates supported particle formation and delivery within a modular system. Engineering TRIM25 domains improved performance. The work establishes a discovery framework in cultured cells, rather than clinical evidence of reduced immunogenicity.
Why it is included: Human-derived carriers offer another route to explore repeated dosing, with biodistribution, manufacturing consistency, and immune responses requiring further study.
Biesel A; Shandheep A; Pavlou A; Busker LM; Koch M; Kopliku V; Maisel K; Boese A; Skerra J; Schröder LJ; Neubert L; Schneider-Daum N; Loretz B; Kalinke U; Lehr CM Journal of controlled release : official journal of the Controlled Release Society · DOI 10.1016/j.jconrel.2026.115509
Lipid-polymer hybrid particles combined polymer stability with lipid-mediated transfection. Hyaluronic acid and polyvinyl alcohol coatings helped preserve particle properties after nebulization, while mucus-covered airway cultures retained measurable transfection. Primary human lung fibroblasts and intratracheally dosed mice provided additional delivery evidence. These results support aerosol formulation development, although intratracheal dosing does not establish the performance of inhaled aerosols in patients.
Why it is included: Addresses both aerosol stress and airway barriers; inhalation deposition, repeated dosing, and disease-specific efficacy remain important translation gaps.
Takayuki Miyazaki; Kenji Kubara; Keita Kondo; Hiroshi Kamiyama; Shoki Hara; Jun Moriya; Hiroshi Ishihara; Yuta Suzuki International Journal of Pharmaceutics · DOI 10.1016/j.ijpharm.2026.127599
A post-loading method combined mRNA with preformed empty lipid nanoparticles using heat and acidic conditions, achieving roughly 90% encapsulation. The particles produced protein expression in mouse liver and spleen, although activity was slightly below conventional microfluidic formulations. Greater payload heterogeneity emerged as a potential limitation; the method supports 96-well preparation.
Why it is included: Simpler preparation could broaden screening access, while payload heterogeneity and potency must be assessed before scaling toward drug development.
Peng Li; Mohammad Abdallah; Yuxin Yao; Rekha Shandre Mugan; Thomas J. Payne; Stewart A. Fabb; Colin W. Pouton; Natalie L. Trevaskis Journal of controlled release : official journal of the Controlled Release Society · DOI 10.1016/j.jconrel.2026.115491
Using three established ionizable lipids, researchers measured RNA, lipid components, lymphatic transport, plasma exposure, and tissue reporter expression in rats. After subcutaneous injection, lymph concentrations exceeded plasma concentrations, but lipid and RNA trafficking did not fully match. The study demonstrates why tracking a lipid label alone may not accurately represent intact RNA delivery or productive expression in tissues.
Why it is included: Provides quantitative guidance for distribution studies; rat reporter experiments and single time-point tissue expression cannot fully predict human therapeutic pharmacokinetics.
Seong Dong Jeong; Chaoyang Tang; Xiaotian Wang; Antoni J. Szeglowski; Yujin Kim; B. J. Kim; Padmanee Sharma; James J. Moon; Wen Jiang; Betty Y. S. Kim Nature Reviews Materials · DOI 10.1038/s41578-026-00974-8
A Perspective proposes designing mRNA vaccine materials around changing immune conditions before and after cancer surgery. The framework considers a broadly applicable preoperative prime followed by a personalized postoperative boost, with carriers controlling expression and immune activation. It is a conceptual design roadmap, not evidence from a new clinical trial.
Why it is included: Formulation teams may need to optimize timing alongside delivery efficiency, generating testable hypotheses for perioperative cancer vaccine development programs.
Kim E; Zenhausern R; Kapadia S; Johnson S; Cho S; Choi J; Park K; Diaz E; Podilapu AR; Kuppan R; Dahlman JE; Kim H; Woo J Molecular therapy : the journal of the American Society of Gene Therapy · DOI 10.1016/j.ymthe.2026.10.024
A ligand-free nanoparticle formulation preferentially delivered mRNA to human hematopoietic stem and progenitor cells in humanized mice without conditioning. It reduced hepatic delivery relative to an SM-102 comparator and enabled functional Cas9-mediated editing of human CD34-positive cells. Single-cell analyses supported tolerability under the conditions examined. Durable stem-cell function and clinical delivery still require further investigation.
Why it is included: Could simplify in vivo hematopoietic gene therapy; humanized-mouse delivery and short-term molecular profiling do not demonstrate durable clinical stem-cell correction.
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.
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.
