messenger RNA

Overview

Messenger RNA (mRNA) is a single-stranded ribonucleic acid that carries genetic information from DNA to the ribosome, where it serves as the template for protein synthesis. In biomedicine, mRNA is of major therapeutic interest because it can be engineered to transiently express proteins without altering the genome, making it useful for vaccines, protein replacement, cancer immunotherapy, and genome-editing delivery systems.

As a therapeutic modality, mRNA is typically formulated in delivery vehicles such as lipid nanoparticles to protect it from degradation and promote cellular uptake. Its clinical and experimental value depends on sequence design, translation efficiency, intracellular stability, and tissue-specific delivery. Recent research has expanded mRNA applications beyond vaccination to include CAR T cell engineering, in situ cancer immunotherapy, organ-targeted gene delivery, and delivery of genome-editing components such as Cas9 mRNA and CRISPR-Cas systems.

Recent Publications Focus

Below is a summary of the newest research publications targeting messenger RNA (sorted by publication date).

Recent studies have focused heavily on improving the delivery, stability, and therapeutic performance of mRNA, most often through lipid nanoparticles (LNPs) and related carrier systems. Several reports examined ways to overcome endosomal entrapment and improve intracellular release, including a light-driven “movable lipid” strategy integrated into a Pfizer-BioNTech BNT162b2 formulation, where programmable mechanical movement was proposed to destabilize endosomal membranes and enhance mRNA-LNP cancer vaccine efficacy. Other work addressed formulation engineering for safer and more effective delivery, such as heparosan-coated LNPs that performed comparably to PEG-modified counterparts with minimal tissue damage and negligible immune activation, and lung-targeted LNPs that achieved high pulmonary selectivity, strong mRNA delivery, and tolerability in repeated dosing. Additional studies explored how lipid composition, nucleic acid length, and manufacturing method affect LNP structure, encapsulation, and scalability, including direct counting of mRNA copies inside individual LNPs, systematic screening of ocular formulations, and a fluidic-oscillator micromixing approach that produced small, highly encapsulated mRNA-LNPs suitable for high-throughput manufacturing.

A major theme across the publications was cell- and tissue-specific targeting of mRNA delivery. Investigators reported improved delivery to primary CD4+ T cells by targeting rapidly cycling receptors CD2 and CD7, and another study used DNA-tethered antibodies to assemble bispecific LNPs that improved T-cell targeting and transfection in vitro and in vivo. Tissue-directed strategies were also described for the lung, retina, pancreas, heart, and colon. In the lung, a simplified Lipid-392 formulation and a separate “tripod-like” lung-targeting lipid platform both enhanced selective delivery, with one study demonstrating IL-10 mRNA activity in acute lung injury. In the retina, formulation screening identified an LNP that improved reporter expression and supported functional Cre mRNA delivery in retinal pigment epithelium. In the pancreas, a capsule-filtration-based LNP enabled pancreas-selective accumulation, Cas9 mRNA and sgRNA delivery, and therapeutic cytokine mRNA delivery in pancreatic cancer models. In the injured heart, a temporal map of mRNA-LNP uptake showed early predominance in myeloid cells and later uptake by fibroblasts, pericytes, endothelial cells, and some cardiomyocytes, depending on dosing time. In the colon, mRNA-loaded LNPs were used to engineer epithelial cells in situ to enhance efferocytosis and reduce intestinal inflammation in mouse colitis models.

Several publications extended mRNA use beyond vaccination into gene editing and disease-modifying therapy. One study delivered mRNA to colonic epithelial cells to promote inflammation resolution, while another used mRNA-LNPs to restore function in familial adenomatous polyposis models, reducing adenoma burden and affecting pathways including nuclear β-catenin localization and downstream oncogenic signaling. A modular peptide carrier was also shown to support mRNA expression in vitro and tumor-associated luciferase expression in vivo, illustrating a non-lipid alternative for systemic gene delivery. In addition, a piezoelectric electroporator called Piezopen was reported to enhance “naked” mRNA, saRNA, and circRNA delivery to skin with robust gene expression and immunogenicity, without systemic inflammation or reactogenicity, suggesting a low-cost alternative to LNP-based vaccination.

Finally, mRNA delivery was increasingly linked to advanced cell engineering and translational manufacturing. A droplet-based mechanoporation platform enabled highly efficient mRNA transfection in primary human T-lymphocytes, including CAR-encoding mRNA delivery, while preserving viability and scalability for engineered cell therapies. Another study showed that mRNA-LNPs functionalized with antibodies targeting CD2 or CD7 could efficiently deliver mRNA to T cells in blood and lymphoid tissue in vivo. Together, these publications emphasize that current mRNA research is centered on improving delivery precision, reducing reactogenicity, enabling tissue-specific expression, and expanding therapeutic applications from vaccination to gene editing, immunomodulation, and cell therapy.

Background PMIDs

• [PMID 41737632]
• [PMID 41787951]
• [PMID 41885077]
• [PMID 41972602]
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• [PMID 41991479]
• [PMID 42015497]
• [PMID 42031024]
• [PMID 42035344]
• [PMID 42135550]
• [PMID 42243120]
• [PMID 42283697]
• [PMID 42396639]
• [PMID 42411346]

Method PMIDs

• [PMID 41786044]
• [PMID 41898718]
• [PMID 41981915]
• [PMID 42012130]
• [PMID 42012185]
• [PMID 42028727]
• [PMID 42068547]
• [PMID 42130331]
• [PMID 42137606]
• [PMID 42151293]
• [PMID 42295617]
• [PMID 42399510]
• [PMID 42401241]
• [PMID 42410237]

Result PMIDs

• [PMID 42084761]
• [PMID 42156430]

Target PMIDs

• [PMID 41640336]
• [PMID 41741655]
• [PMID 41791459]
• [PMID 41845088]
• [PMID 41916505]
• [PMID 41931102]
• [PMID 41933803]
• [PMID 41975643]
• [PMID 42064372]
• [PMID 42066072]
• [PMID 42070739]
• [PMID 42117531]
• [PMID 42132777]
• [PMID 42138142]
• [PMID 42154259]
• [PMID 42210530]
• [PMID 42384808]
• [PMID 42386746]
• [PMID 42412769]

Conclusion PMIDs

• [PMID 41892063]