Platelets contribute to a variety of physiological processes, including inflammation, sepsis, and cancer. However, because of their primary role in hemostasis, platelet transfusions are largely restricted to managing thrombocytopenia and bleeding. One way to expand the utility of platelet transfusions would be to genetically engineer donor platelets with new or enhanced functions. We have previously shown that lipid nanoparticles containing mRNA (mRNA-LNP) can be used to genetically modify authentic platelets in a nonclinical crystalloid solution. Currently, platelets collected for transfusion are stored in plasma or in plasma supplemented with platelet additive solution (PAS) at supraphysiological concentrations at room temperature, or at 4°C if intended for use in acute hemorrhage. Here, we describe a new plasma-optimized mRNA-LNP for transfecting platelets directly in plasma and plasma supplemented with PAS that is scalable to physiological and supraphysiological platelet concentrations. Transfecting platelets in clinical solutions with mRNA-LNP does not affect aspects of in vitro physiology, and transfected platelets are storable. The compatibility of this transfection system with current clinical practices could enable future mRNA-LNP–based platelet products and cell therapies.

中文翻译：

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使用 mRNA-脂质纳米颗粒对可转血血小板进行基因工程与血站实践兼容


血小板有助于多种生理过程，包括炎症、败血症和癌症。然而，由于血小板输注在止血中起主要作用，因此血小板输注主要限于控制血小板减少症和出血。扩大血小板输注效用的一种方法是对供体血小板进行基因工程改造，使其具有新的或增强的功能。我们之前已经表明，含有 mRNA （mRNA-LNP） 的脂质纳米颗粒可用于在非临床晶体溶液中对真实的血小板进行基因修饰。目前，为输血而采集的血小板在室温下以超生理浓度储存在血浆或补充血小板添加剂溶液 （PAS） 的血浆中，如果用于急性出血，则储存在 4°C 下。在这里，我们描述了一种新的血浆优化的 mRNA-LNP，用于直接在血浆和补充有 PAS 的血浆中转染血小板，其可扩展到生理和超生理血小板浓度。用 mRNA-LNP 在临床溶液中转染血小板不会影响体外生理学的各个方面，并且转染的血小板是可储存的。该转染系统与当前临床实践的兼容性可能使未来基于 mRNA-LNP 的血小板产品和细胞疗法成为可能。