Zhang and colleagues engineered the poly(A) tail as a programmable regulatory element, showing that embedding cell-type-specific microRNA target sites directly within it confers robust, position-dependent silencing in off-target tissues while preserving activity in target cells. This strategy offers a new modular tool to enhance mRNA therapeutic safety and precision.

Kis and colleagues report an integrated sequential-batch IVT–oligo-dT process that links RNA synthesis and affinity capture through a shared buffer, enabling direct crude-IVT loading and flowthrough recycling. The workflow improves cap-analog utilization and raw-material efficiency while preserving functional mRNA expression across five cycles.

COL17A1 nonsense mutations generate premature termination codons, reducing collagen XVII through truncated protein production and/or nonsense-mediated decay (NMD), and causing junctional epidermolysis bullosa. Translational readthrough drug offers a potential approach to nonsense mutations suppression. Different COL17A1 nonsense mutations showed distinct responses to readthrough drugs and NMD inhibitors, supporting personalized therapeutic strategies.

Small extracellular vesicles from differentiating human skeletal muscle cells are enriched in miR-193b-3p, which contributes to myogenic responses through AP2M1 regulation. These findings establish a miR-193b-3p–AP2M1 axis connecting extracellular vesicles to muscle regeneration and highlight its potential role in regulating myogenic processes.

CRISPR hybrid guides containing RNA and DNA nucleotides (chRDNA) enhance Cas nuclease specificity by reducing off-target editing. Intravenous administration of LNP-encapsulated Cas12a mRNA with a chRDNA guide in mice led to dose-responsive hepatic genome editing without detectable off-target editing and near elimination of the targeted plasma protein for one year.

Immunization with a nucleoside-modified mRNA-LNP vaccine encoding the conserved malaria antigen E140 induced durable humoral immunity in mice and generated invasion-blocking antibodies against Plasmodium vivax. The results highlight E140 as a promising candidate for next-generation malaria vaccines.

Et1Ψ-modified mRNA shows UUU-dependent translational sensitivity, but targeted UUU-to-UUC recoding restores protein expression. With this sequence constraint addressed, Et1Ψ reduces early innate immune activation while preserving vaccine-induced humoral, cellular, and neutralizing responses, thereby establishing codon–modification compatibility as a practical design principle for mRNA therapeutics.

Lipid nanoparticles incorporating DOTAP and DOPE enable serial mRNA transfection of primary human T cells with significantly improved viable cell yields compared to standard electroporation. This platform supports iterative functional modifications across multiple rounds of delivery while preserving cell viability, facilitating the manufacturing of complex, multi-payload cell therapies.

Tang and colleagues systematically review the structural biology, synthetic engineering, and immunological consequences of the mRNA 5' cap. By analyzing how Cap-0 through Cap-2 methylation patterns differentially affect translation and immune recognition, this work highlights the conceptual advances and translational potential of cap engineering for next-generation vaccines.

TTN truncating variants cause dilated cardiomyopathy and may be amenable to therapeutic upregulation. Disrupting TTN upstream open reading frames (uORFs) increased luciferase reporter expression, however disrupting endogenous uORFs in hiPSC-derived cardiomyocytes did not increase titin protein. This highlights the importance of validating regulatory mechanisms in disease-relevant cellular contexts.

Ionizable lipid components of LNP vaccine formulations play an integral role in providing the necessary immune stimulatory signals required for effective anti-tumor T cell responses. This study finds that inclusion of a novel ionizable lipid confers effective tumor control in part through the generation of type I interferons.

Gene therapy is transforming hereditary hematological disorders. This review summarizes approved gene addition, editing, and silencing strategies for sickle cell disease, thalassemia, and hemophilia, highlights curative potential, and discusses remaining challenges such as immune responses, cost, and accessibility

Circular RNAs (circRNAs) have emerged as promising next-generation therapeutic platforms due to their exceptional stability, prolonged protein expression, and low immunogenicity. This review highlights advances in enzymatic, chemical, and bio-orthogonal circRNA synthesis, compares their advantages and limitations, and discusses emerging applications in vaccines, cancer therapy, and precision medicine.