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.
Chun K; Choi SY; An K; Jo DH; Lee H Journal of controlled release : official journal of the Controlled Release Society · DOI 10.1016/j.jconrel.2026.115453
A C12-200-based formulation was optimized for movement and cellular delivery in the protein-poor vitreous environment. It co-delivered RB1 mRNA and triptolide, improving antiproliferative activity and suppressing tumors in an orthotopic retinoblastoma model after intravitreal administration. Retinal evaluations supported tolerability during the study period. The combination remains preclinical and requires longer ocular safety assessment and pediatric translation studies.
Why it is included: Demonstrates tissue-environment-specific engineering for ocular combination therapy; animal tumor suppression and short-term retinal assessments do not establish pediatric clinical safety.
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.
Abdulraouf M. Abbas; Ramy Ghanim; Sebastian Rudden; David Schultz; Bora Jang; Avraham Shakked; Hyejin Kim; James E. Dahlman; Alex Abramson ACS nano · DOI 10.1021/acsnano.5c18549
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.
Why it is included: Shows how gastrointestinal administration can redirect distribution; submucosal delivery in rodents is distinct from a validated oral capsule or human metabolic therapy.
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.
Ha M; Kim J; Kim S; Naidu GS; Cho S; Yong SB Advanced science (Weinheim, Baden-Wurttemberg, Germany) · DOI 10.1002/advs.77923
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.
Why it is included: Combines delivery engineering with checkpoint modulation; evidence from two lipid backbones does not establish universal targeting or clinical superiority.
Yuxin He; Lin Wang; Abigael P. Williams; Trisha I. Valerio; Yuanhong Sun; James Bowman; Samantha D. Ricketts; Savannah Hammond; Aidan Sison; Jezan Alexandre; Zachary Niastor; Wei R. Chen; Dixy E. Green; Kar-Ming Fung; Paul L. DeAngelis; Stefan Wilhelm ACS nano · DOI 10.1021/acsnano.6c11865
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.
Why it is included: Expands surface-engineering options for immune delivery; trafficking correlations and short-term mouse tolerability do not establish long-term human safety or universal PEG replacement.
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.
Why it is included: Adds spatial RNA arrangement to formulation design; vaccine gains were demonstrated in mice and require independent replication and clinical validation.
Nageen Sardar; Shoaib Manzoor Human immunology · DOI 10.1016/j.humimm.2026.112083
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.
Why it is included: Useful for comparing next-generation RNA platforms; heterogeneous studies and limited clinical data prevent broad claims of superior durability or safety.
Rui Chen; Letao Xu; Alexander H. Staudacher; Xing Wang; Ruoxuan Jia; John W. Finnie; Xiaoyan Wang; Dawn M. Whelan; Michael P. Brown; Chun-Xia Zhao Science advances · DOI 10.1126/sciadv.aed9568
Antibody-coated nanoparticles targeted TREM2-expressing tumor-associated macrophages and combined CXCL9-encoding mRNA with a Toll-like receptor agonist. The approach remodeled the tumor immune environment and increased cytotoxic T-cell infiltration and activity. Additional checkpoint blockade strengthened immune responses in experimental models. This is a targeted delivery and combination-immunotherapy proof of concept, rather than evidence of efficacy in patients.
Why it is included: Connects macrophage targeting with local chemokine production; animal combination-treatment findings do not establish clinical benefit or the contribution of each component.
Seong Gi Lim; Minju Lee; Yiming Wang; Eunjin Choi; Ji Sun Park; Kyungmin Park; Hayoung Jeon; Donghyun Kim; Donghyun Lee; Yeeun Lee; Kee‐Pyo Kim; Eunha Kim; Heebeom Koo Advanced science (Weinheim, Baden-Wurttemberg, Germany) · DOI 10.1002/advs.77387
The study introduces an ionizable lipid with two apparent ionization transitions that persist after nanoparticle formulation. Following intravenous administration, the particles favored pulmonary mRNA expression and improved outcomes in an experimental acute lung inflammation model. Simulations linked protonation states to membrane interactions. The work provides a mechanistic design hypothesis, with selectivity and tolerability established only in the tested preclinical settings.
Why it is included: Links ionization behavior to lung expression and intracellular release; mechanistic simulations and mouse efficacy require broader validation before translation.
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.
Electrically neutral self-assembling peptides were developed as mRNA vehicles that form RNA-containing nanotubular assemblies. Experiments examined delivery alongside cytotoxicity and membrane-disruption behavior, reporting favorable readouts in tested systems. This is an alternative peptide carrier rather than an LNP formulation. The peer-reviewed early article supports further development, but its title should not be interpreted as universal or clinical nontoxicity.
Why it is included: Broadens the carrier landscape beyond lipids; long-term tolerability, biodistribution, and therapeutic performance require further preclinical and clinical investigation.
