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Research Literature

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mRNA / LNP 67

Duplicate DOIs are merged. This is a selected collection, not an exhaustive bibliography.

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Original research
International journal of pharmaceutics

Nebulization-stable lipid-polymer hybrid nanoparticles for mRNA delivery in advanced in vitro respiratory models

Hassoun H; Pascarel C; Erny A; Giang E; Garapon C; Gerossier L; Coiffier C; Monge C; Verrier B; Archer F; Aznar N

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.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1016/j.ijpharm.2026.127550

Methods
ACS Nano

In Vivo Blood Kinetics and Transcript Integrity of Three mRNA–Lipid Nanoparticle Vaccines in Humans

Stephen J. Kent; Shiyao Li; Thakshila H. Amarasena; Arnold Reynaldi; Michael G. Leeming; Jennifer A. Juno; Adam K. Wheatley; Georgia Deliyannis; Dale I. Godfrey; Terry Nolan; Colin W. Pouton; Miles P. Davenport; Yi Ju

Serial blood samples from 73 vaccine recipients were analyzed using ddPCR for total and long-range-linked mRNA and LC-MS for ionizable lipids. RNA and lipid decay differed across three vaccine platforms. Cohorts differed in dose, vaccination history, and sampling schedules. Detecting circulating RNA fragments does not by itself establish continued protein expression, clinical toxicity, or comparative vaccine effectiveness.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1021/acsnano.6c09226

Original research
Drug delivery and translational research

PEG-associated efficacy loss in lipid nanoparticles persists across formulation modifications for mRNA delivery

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

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.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1007/s13346-026-02225-3

Original research
Nature Communications

Interpretable AI-guided discovery of degradable ionizable lipids with enhanced hepatic mRNA delivery in vivo

Zhen Zhang; Yongbo Ren; Deqiang Kong; Jindong Feng; Kaiyi Hu; Xinyun Xu; Fukang Deng; Peixia Li; Jiuao Wang; Wenhui Huang; Guodan Wei; Yang Su; Ying Tan; Shuixing Zhang; Xiaodan Sun; Feiyu Kang; Hao Yan

Researchers combined a 520-member degradable lipid library with interpretable machine learning and a 10,920-member virtual design space. Independent mouse experiments identified PA97MD101 as a lead for hepatic mRNA expression, Cre-mediated recombination, and Cas9-based TTR suppression. The study links screening predictions with functional animal validation, without establishing clinical safety or efficacy.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1038/s41467-026-78635-1

Original research
Science China. Life sciences

Optimization of lipid nanoparticles reduces hepatic accumulation and enhances local delivery of mRNA

Yue Ma; Yaoxian Han; Jiawei Zhou; Yuxin Xiao; Jie Liu; Wenjie Sun; Hui Yang; Guangyu Hu; Shangang Li; Weizhi Ji; Wenting Guo; Lei Zhang; Yongchang Chen

A design-of-experiments approach produced an SM-102-derived formulation with less hepatic reporter expression and preserved or improved expression after local administration. Experiments included intramuscular, intracerebroventricular, and intravitreal routes. Mechanistic analyses associated the change with altered protein binding, systemic exposure, and hepatocyte trafficking. These route-specific results support formulation optimization but do not demonstrate noninvasive access to the brain or eye.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1007/s11427-025-3541-0

Original research
Journal of the American Chemical Society

Circular RNA Delivery In Vitro and In Vivo Using Doubly Branched Aminoethoxy-Functionalized Ionizable Lipid Nanoparticles

Adam Cook; Pavan K. Yadav; Ekram W. Helmy; Kseniia Vlasova; Howard Y. Chang; Paul A. Wender

A study designed ionizable lipids specifically for circular RNA, whose topology differs from linear mRNA. Lead lipid iL-19 combined aminoethoxy head groups with doubly branched tails and improved protein expression after intramuscular delivery in mice relative to several benchmark lipids. The results establish preclinical design principles, not clinical superiority.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1021/jacs.6c14175

Original research
Journal of controlled release : official journal of the Controlled Release Society

Lipid nanoparticle-mediated co-delivery of human RB1 mRNA and triptolide for localized genetic therapy of retinoblastoma

Chun K; Choi SY; An K; Jo DH; Lee H

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.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1016/j.jconrel.2026.115453

Original research
Journal of virology

A multivalent mRNA-lipid nanoparticle vaccine containing eight hemagglutinin antigens elicited broad neutralizing antibody responses and protected against influenza A virus challenge in swine

Ciacci Zanella G; Vincent ML; Flores L; Aljets EK; Paiva RC; Markin A; Inderski B; Dwivedi G; Weissman D; Wymore Brand M; Santos JJS; Hensley SE; Anderson TK; Gauger PC; Baker AL

Researchers selected eight hemagglutinin sequences to represent circulating swine influenza diversity and evaluated individual and multivalent mRNA vaccines in pigs. The multivalent formulation elicited responses against its component antigens and protected against lung lesions after the tested challenge. This large-animal veterinary study supports adaptable multivalent design, while protection across untested strains and direct relevance to human influenza remain unresolved.

mRNA / LNP
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DOI: 10.1128/jvi.00848-26

Original research
Vaccine

Circular RNA vaccines encoding Pvs25 induce antibodies that block Plasmodium vivax transmission

Nawapol Kunkeaw; Wang Nguitragool; Thitipa Thosapornvichai; Nattawut Buasri; Suradej Hongeng; Eizo Takashima; Takafumi Tsuboi; Patompon Wongtrakoongate; Jetsumon Sattabongkot

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.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1016/j.vaccine.2026.129221

Original research
iScience

Lipid-based mRNA chimeric antigen receptor T cells for enhanced <i>in vitro</i> antitumor activity

Haixia Gao; Yuan Fang; Zhidan Tian; Chuanxin Guo; Pei Wang; Tao Liu; Yan Sun; Pingjing Zhang; Qijun Qian

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.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1016/j.isci.2026.117390

Reviews & perspectives
Discover Pharmaceutical Sciences

A review of analytical techniques for characterization of mRNA drug substance in therapeutics and their suitability as a multi-attribute method

Kyle J. Tynan; Karndeep Singh; Trina Mouchahoir; Mark S. Lowenthal; Karen W. Phinney

This review evaluates electrophoresis, chromatography, sequencing, and mass spectrometry for measuring mRNA drug-substance identity, length, concentration, intactness, and purity. It compares throughput, sample preparation, and total analysis time while considering multi-attribute methods used for protein therapeutics. The authors identify opportunities for integrated mRNA analytics, rather than validating a universal platform that replaces all individual quality assays.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1007/s44395-026-00058-0

Original research
Journal of controlled release : official journal of the Controlled Release Society

Protein expression kinetics of mRNA, saRNA, and pDNA as individual or co-delivered payloads using a common lipid nanoparticle formulation

McMillan C; Hussain M; Punnabhum P; Varley AJ; Kong KYS; Rattray Z; Druschitz A; Perrie Y

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.

mRNA / LNP
Read guide →Original paper ↗

DOI: 10.1016/j.jconrel.2026.115418

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