Find research, methods, and reviews across our scientific fields.
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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.
DOI: 10.1038/s41565-026-02326-7
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.
DOI: 10.1038/s41467-026-79039-x
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.
DOI: 10.1016/j.ijpharm.2026.127599
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.
DOI: 10.1016/j.jconrel.2026.115509
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.
DOI: 10.1038/s41587-026-03343-6
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.
DOI: 10.1016/j.jconrel.2026.115491
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.
DOI: 10.1038/s41578-026-00974-8
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.
DOI: 10.1016/j.ymthe.2026.10.024
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.
DOI: 10.1016/j.ymthe.2026.10.021
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.
DOI: 10.1016/j.xphs.2026.104556
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.
DOI: 10.1038/s44321-026-00537-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.
DOI: 10.1038/s41541-026-01581-y
