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MRNA / LNP / RESEARCH LIBRARY
Important mRNA/LNP publications from the past 120 days
Search bilingual publication guides on delivery, in vivo CAR-T, therapeutic translation, safety, analytics, and manufacturing.
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.
Journal of controlled release : official journal of the Controlled Release Society
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.
Investigators administered nanoparticles to several gastrointestinal submucosal sites to examine route-dependent targeting. Gastric delivery increased pancreatic exposure in rodents, while GLP-1 mRNA improved glucose regulation in mice. Buccal administration supported local and lymphatic targeting with vaccine responses. These are tissue-directed administration experiments; they do not establish that conventional swallowed nanoparticles can survive digestion and reproduce the same delivery profile.
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.
Researchers modified buffer exchange into a two-step dialysis process, first promoting fusion under acidic, higher-ionic-strength conditions while retaining ethanol, then removing ethanol and raising pH. Compared with one-step exchange, the process increased mRNA copies per particle, reduced empty particles, and improved transfection in cells and animals. These formulation-specific results do not establish that removing empties always improves every product.
Researchers incorporated an amphiphilic PD-L1 inhibitor as an additional nanoparticle component rather than administering it separately. The modified formulation increased lymph-node reporter expression and strengthened vaccine-associated immune responses in experimental models. Similar targeting effects were observed with two ionizable lipid backbones. These results suggest formulation-dependent immune targeting, without proving broad applicability or clinical benefit across tumor types.
Researchers compared 12 lyophilized mRNA-LNP formulations containing sucrose, trehalose, and polyvinylpyrrolidone. A ternary protectant system at a 1:20 lipid-to-protectant ratio preserved particle properties, RNA integrity, and in vitro transfection after one month at 40°C. Sucrose crystallization reduced protection. The results show why physical measurements need functional confirmation and do not establish a clinical product shelf life.
Heparosan surface modification was compared with conventional PEG-based nanoparticles across several ionizable lipid formulations. Modified particles improved expression in immune-cell models and showed reduced association with late endosomes and lysosomes. Mouse experiments assessed repeated expression and vaccine antibody responses. The findings support an alternative surface-engineering approach, while long-term immunogenicity, biodistribution, and manufacturing consistency require additional study.
Arcturus reported interim Phase 2 findings for ARCT-810 in ornithine transcarbamylase deficiency, including lower or maintained-normal fasting ammonia and reduced glutamine, with generally favorable tolerability. The company plans to incorporate next-generation ARCT-2601 into an amended protocol near year-end. Separately reported large expression gains for its new delivery platform came from nonhuman-primate studies, not comparative human efficacy data.
ExploRNA and the Łukasiewicz Industrial Chemistry Institute announced a partnership to advance GMP-quality manufacturing of proprietary mRNA cap analogs, including AvantCap Q1. The collaboration combines capping technology with chemical synthesis and production scale-up to support clinical-stage mRNA vaccines and therapeutics. The announcement did not disclose financial terms or establish that newly manufactured batches had already been delivered to customers.
Researchers reorganized preformed nanoparticles so a metabolic RNA becomes available before the therapeutic payload. This staged architecture increased cellular energy availability and subsequent protein production. Mouse cancer and infectious-disease vaccine experiments showed improved immune activity, supporting spatial organization as an additional delivery design variable. Compatibility across several nucleic acid formats was demonstrated, but human performance remains untested.
This review compares self-amplifying and circular RNA vaccine architectures, expression kinetics, delivery approaches, and immune responses. It discusses the different reasons these platforms may extend antigen production or reduce dose requirements, alongside manufacturing, purity, reactogenicity, and regulatory challenges. It is a synthesis of heterogeneous preclinical and early clinical evidence, not a new head-to-head trial establishing superiority over conventional mRNA vaccines.
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