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.
Jefferson J. S. Santos; Carine K. Souza; Giovana C. Zanella; Débora B. Goulart; Bailey Arruda; Paola Boggiatto; Mitchell V. Palmer; Celeste A. Snyder; Michaela A. Kristula; Charlene Dickens; Terry L. Webb; Reilly K. Atkinson; Bernadeta Dadonaite; Garima Dwivedi; Mohamad-Gabriel Alameh; Christopher A. Hunter; Lisa A. Murphy; Jesse D. Bloom; Drew Weissman; Gary C. Althouse; Amy L. Baker; Scott E. Hensley Nature Biotechnology · DOI 10.1038/s41587-026-03343-6
An experimental H5N1 mRNA-LNP vaccine was tested in eight lactating dairy cows split between vaccinated and control groups. After two doses and mammary challenge, vaccination reduced peak viral RNA in milk by about 1,000-fold and lessened mastitis and fibrosis. This small animal study does not establish field effectiveness or human protection.
Why it is included: The findings broaden RNA vaccine applications to livestock, while larger field studies, manufacturing economics, and regulatory requirements remain important.
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.
Wang G; Guo Y; Guo K; Zhang C; Zhou Y; Xia J; Jiang H; Liu J; Ren J; Mohamed AO; Tang K; Chen X; Sun S; Xing Y; Yang Y; Shen M; Wang R; Huang Y; Li X; Lin A Molecular therapy : the journal of the American Society of Gene Therapy · DOI 10.1016/j.ymthe.2026.10.021
An engineered nanoparticle delivered mRNAs encoding IL-1 receptor antagonist and an angiopoietin-like 3 derivative through intra-articular injection. The combination addressed inflammation and cartilage degeneration in several mouse arthritis models, with transcriptomic analyses supporting complementary biological effects. These findings broaden local mRNA therapy beyond vaccination, but durable structural benefit, repeated-dose safety, and effectiveness in human joints remain unproven.
Why it is included: Explores local protein replacement for two joint-disease processes; mouse models cannot establish durable cartilage regeneration or disease modification in patients.
Carlos Victor Montefusco-Pereira Journal of Pharmaceutical Sciences · DOI 10.1016/j.xphs.2026.104556
A minireview distinguishes bulk encapsulation efficiency from particle occupancy and RNA copy-number distributions. High encapsulation efficiency can coexist with RNA-negative particles, and process changes may alter loading without changing average size. The author cautions that eliminating empty particles does not necessarily improve activity; product-specific evidence must establish whether occupancy is a critical quality attribute.
Why it is included: Particle-level measurements could strengthen characterization and comparability, but routine specifications need validated methods and a demonstrated relationship to product performance.
Yao Zhang; Yu Qin; Zhongbing Qi; Qingzhe Yang; Xian Zhang; Shichuan Hu; Yuejun Li; Boduan Xiao; Jianchuan Hu; Ping Cheng EMBO Molecular Medicine · DOI 10.1038/s44321-026-00537-y
A mouse study compared LNP-delivered self-amplifying RNA and an Ad5 vaccine encoding the same RSV prefusion F antigen. Intramuscular dosing produced distinct immune patterns: saRNA favored pulmonary mucosal and tissue-resident memory responses, while Ad5 generated stronger systemic responses. The comparison concerns immune architecture, not demonstrated superiority in human protection.
Why it is included: Respiratory vaccine development should assess tissue-localized immunity alongside serum responses, rather than selecting platforms solely on systemic antibody measurements.
Abby L. Martin; Jessica F. Cotterell; Kaitlin H. Buick; Thomas W. Bird; Joanna Kuang; Olga R. Palmer; Ngarangi C. Mason; Lydia White; Sarah L. Draper; Amy J. Foster; Gavin F. Painter; Isabelle Montgomerie; Tifany Oulavallickal; Wayne M. Patrick; Lisa M. Connor npj Vaccines · DOI 10.1038/s41541-026-01581-y
Researchers separated the effects of circular structure, preparation quality, and nucleotide modification across two vaccine antigen systems. Cleaner circular RNA preparations caused less innate immune activation, but antibody and T-cell response levels were comparable with linear mRNA. Incorporating m6A was associated with higher antibody avidity, rather than a general increase in expression.
Why it is included: Circular RNA developers should prioritize impurity control and functional immune measurements when evaluating manufacturing choices and claims of platform advantages.
