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.
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.
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.
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.
Circular RNA nanoparticles encoding the malaria transmission antigen Pvs25 were compared with a modified linear mRNA vaccine in mice. Both platforms induced antigen-specific responses, and booster immunization generated antibodies that blocked parasite development in mosquito assays. The findings support further evaluation of circular RNA for transmission-blocking vaccination, without establishing greater efficacy, durability, or manufacturing economy than linear mRNA in humans.
Why it is included: Extends circular RNA vaccine evidence beyond common viral targets; mouse immunogenicity and mosquito assays require confirmation in larger animals and humans.
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.
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.
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.
Simin Chun; Hyorim Nam; Donghyun Lee; Yeeun Lee; Cheol Hui Park; Chaehwan Lim; Donghyun Kim; Ji Sun Park; Kee-Pyo Kim; Hak Soo Choi; Heebeom Koo Journal of the American
Chemical Society · DOI 10.1021/jacs.6c13674
Visible-light-driven multicomponent synthesis generated 275 branched amine-containing ionizable lipids from modular building blocks. The platform linked one-pot synthesis with purification-free cell screening and subsequent animal evaluation. A lead lipid improved expression relative to the tested MC3 formulation, and formulation adjustment enabled organ-selective delivery. The work accelerates discovery but does not establish a clinically optimized or validated manufacturing process.
Why it is included: Expands lipid chemical diversity with a practical screening workflow; lead superiority is comparator-dependent and requires further translational development.
This CMC review connects lipid chemistry and manufacturing parameters with critical quality attributes in mRNA-LNP development. It compares microfluidic scale-out with impinging-jet scale-up and emphasizes orthogonal analytics, stability in plasma or serum, lipid impurities, and RNA–lipid adducts. Early comparability planning is recommended. The framework does not demonstrate that one carrier or manufacturing platform is universally superior.
Why it is included: Helps connect discovery formulations with development requirements; particle size and encapsulation alone cannot establish a complete manufacturing control or comparability strategy.
Beom Kyu Kim; Ji-Hyun Park; Won-Suk Choi; Sol Oh; Se Hee An; Gi Chan Lee; Santosh Chokkakula; Chang-Ung Kim; Ju Hwan Jeong; Seong Cheol Min; Dong Gyu Lee; Ju Ryeong Lee; Sun-Woo Yoon; Doo-Jin Kim; Timothy J. Mahony; Richard J. Webby; Young Ki Choi; Yun Hee Baek; Min-Suk Song Molecular Therapy · DOI 10.1016/j.ymthe.2026.07.047
A Coxsackievirus B5 replicon used internal ribosome entry site-driven translation to generate a capless self-amplifying RNA vaccine. Genetic optimization improved expression, and LNP-formulated H5 antigen constructs induced neutralizing antibodies and cellular responses in mice. Low-dose vaccination protected against lethal H5N8 challenge. The platform changes capping requirements, but human immunogenicity, manufacturing performance, and safety remain unestablished.
Why it is included: Introduces a cap-independent saRNA architecture with mouse dose-sparing evidence; clinical dosing and process advantages have not yet been demonstrated.
Jin-He Liu; Jian Zang; Jing-Ru Xu; Xue-Bin Ran; Min Su; Wang-Ming Zhang; Zhang-Wen Ge; Qiao-Yang Sun; Ling-Wen Ding Journal of Biomedical Science · DOI 10.1186/s12929-026-01277-4
This review examines mRNA therapy and impurity control during in vitro transcription, focusing on purification strategies and double-stranded RNA removal. It compares detection and separation approaches with attention to RNA integrity, recovery, and manufacturing feasibility. Construct-specific differences and analytical limitations complicate direct comparisons; the review does not establish a universal acceptable dsRNA limit for every product.
Why it is included: Useful for selecting purification and impurity assays; product specifications still require validated measurement capabilities and evidence linking impurities to biological risk.
