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.
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.
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.
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.
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.
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.
McMillan C; Hussain M; Punnabhum P; Varley AJ; Kong KYS; Rattray Z; Druschitz A; Perrie Y Journal of controlled release : official journal of the Controlled Release Society · DOI 10.1016/j.jconrel.2026.115418
Using a common ALC-0315 formulation, the study compared reporter expression from conventional mRNA, self-amplifying RNA, and plasmid DNA, individually and in combinations. Mouse experiments showed distinct timing and duration associated with payload identity. Mixed preparations generally behaved additively under the tested conditions. The work helps separate cargo effects from formulation effects, without establishing universal expression profiles across doses, tissues, or products.
Why it is included: Improves interpretation of payload-dependent expression kinetics; one formulation and reporter system cannot define performance across all therapeutic cargoes or routes.
Songtao Dong; Fanglin Gong; Tyler Thomson; Yunshu Cai; Lauren Healy; Rick X. Z. Lu; Ziyu Zhou; Yue Xu; Jingan Chen; Margarita Savguira; Xianglei Fu; Sijin Luozhong; Muye Zhou; Payton Kirtley; Brandon K. Wilder; Bowen Li Nature biotechnology · DOI 10.1038/s41587-026-03298-8
A lipid screen explicitly incorporated a large base-editor transcript rather than relying on small reporter RNA. The lead lipid retained favorable RNA interactions and membrane-disrupting structure as cargo size increased. It improved editing in liver, brain, and lung using different administration routes, including intrathecal and intratracheal dosing. The findings do not establish systemic delivery to all three organs.
Why it is included: Makes cargo size a practical screening parameter for gene-editing formulations; tissue results depend on administration route and remain preclinical.
Ao Hoi Tong; Haichao Zhu; Chenming Zou; Bingshu Liang; Xueer Wu; Shengrong Guo International journal of biological macromolecules · DOI 10.1016/j.ijbiomac.2026.154367
An injectable hydrogel co-delivered hyaluronidase and light-responsive nanoparticles carrying IL-12 and GM-CSF mRNAs. The design combined stromal remodeling, local retention, and photoactivated intracellular delivery. In a postoperative mouse breast-cancer model, treatment reduced recurrence and altered local and systemic immune responses. The multiple-component system remains experimental, with light access, long-term safety, and clinical feasibility requiring further work.
Why it is included: Integrates extracellular and intracellular delivery strategies after surgery; a mouse recurrence model and short-term safety checks cannot establish clinical recurrence prevention.
