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Platelet transfusions are essential for managing bleeding and hemostatic dysfunction and could be expanded as a cell therapy due to the multifunctional role of platelets in various diseases. Creating these cell therapies will require modifying transfusable donor platelets to express therapeutic proteins. However, there are currently no appropriate methods for genetically modifying platelets collected from blood donors. Here, we describe an approach using platelet-optimized lipid nanoparticles containing mRNA (mRNA-LNP) to enable exogenous protein expression in human and rat platelets. Within the library of mRNA-LNP tested, exogenous protein expression did not require nor correlate with platelet activation. Transfected platelets retained hemostatic function and accumulated in regions of vascular damage after transfusion into rats with hemorrhagic shock. We expect this technology will expand the therapeutic potential of platelets.
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http://dx.doi.org/10.1126/sciadv.adi0508 | DOI Listing |
Nano Lett
September 2025
Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, China.
Interleukin-12 (IL-12) is a robust proinflammatory cytokine that activates immune cells, such as T cells and natural killer cells, to induce antitumor immunity. However, the clinical application of recombinant IL-12 has been limited by systemic immune-related adverse events (irAEs) and rapid degradation. To address these challenges, we employed mRNA technology to encode a tumor-activated IL-12 "lock" fusion protein that offers both therapeutic efficacy and systemic safety.
View Article and Find Full Text PDFHepatology
September 2025
Department of Pathology, Department of Molecular Biology, Moores Cancer Center, University of California San Diego, La Jolla, CA 92037, USA.
Background And Aims: So far, there is no effective mechanism-based therapeutic agent tailored for liver tumors. Immune checkpoint inhibitors (ICIs) have demonstrated limited efficacy in liver cancer, often associated with severe adverse effects. Although poly-inosinic:cytidylic acid (polyIC) has shown an adjuvant effect when combined with anti-PD-L1 antibody (αPD-L1) in treating liver tumors in animal models, its systemic toxicity limits its clinical utility.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
June 2025
Key Laboratory of RNA Innovation, Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Lipid nanoparticles (LNPs) are lead non-viral vectors for delivering nucleic acids. LNPs can efficiently encapsulate nucleic acids, protect them from degradation, enhance cellular uptake and induce endosome escape, which show high transfection efficiency and low immunogenicity. In this review, we first introduce the LNP components, highlighting their critical roles in encapsulation, stability, delivery efficiency, and tissue tropism.
View Article and Find Full Text PDFInt J Nanomedicine
September 2025
Department of Pharmaceutics, Crescent School of Pharmacy, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai, Tamilnadu, India.
Hepatocellular carcinoma (HCC) is a major global health issue, ranking as the sixth most common cancer and a leading cause of cancer-related deaths worldwide. Risk factors for HCC include chronic hepatitis B and C, obesity, alcohol abuse, diabetes, and metabolic disorders. Current treatments, such as surgery, transplantation, and chemotherapy, are often ineffective in advanced stages due to tumor resistance and the inability to target key oncogenic pathways.
View Article and Find Full Text PDFMol Ther Nucleic Acids
September 2025
Sanofi, 1541 Avenue Marcel Mérieux, 69280 Marcy l'Etoile, France.
Messenger ribonucleic acid (mRNA), a promising tool in vaccine and therapeutic development, is reliant on intact mRNA delivery into target cells. Given its susceptibility to degradation, ensuring its stability is crucial, necessitating rigorous quality control throughout the product life cycle. This study presents an ion-pair reverse-phase liquid chromatography method that enables rapid and direct mRNA extraction from lipid nanoparticles, facilitated by using a surfactant in the sample preparation.
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