具有 mRNA-脂质纳米颗粒的可输血血小板的基因工程与血库实践兼容。
Genetic Engineering of Transfusable Platelets with mRNA-Lipid Nanoparticles is Compatible with Blood Banking Practices.
发表日期:2024 Aug 27
作者:
Colton Strong, Jerry Leung, Emma Kang, Katherine E Badior, Madelaine K Robertson, Nicolas Pereyra, Elyn Marie Rowe, Amanda Wietrzny, Brenda Ma, Zechariah Noronha, Deaglan Arnold, Marco A Ciufolini, Dana V Devine, Eric Jan, Pieter R Cullis, Christian J Kastrup
来源:
BLOOD
摘要:
血小板有助于多种生理过程,包括炎症、败血症和癌症。然而,由于血小板输注的主要作用是止血,因此血小板输注在很大程度上仅限于治疗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改造,使其具有新的或增强的功能。我们之前已经证明,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血小板进行基因修饰。目前,收集用于输血的血小板在室温下储存在血浆中或补充有超生理浓度的血小板添加剂溶液 (PAS) 的血浆中,如果打算用于急性出血,则储存在 4 ℃ 下。在这里,我们描述了一种新的血浆优化 mRNA-LNP,用于直接在血浆和补充有 PAS 的血浆中转染血小板,可扩展到生理和超生理血小板浓度。用mRNA-LNP转染临床溶液中的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以使未来基于 mRNA-LNP 的血小板产品和细胞疗法成为可能。版权所有 © 2024 美国血液学会。
Platelets contribute to a variety of physiological processes including inflammation, sepsis and cancer. However, due to 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 non-clinical 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 ºC 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.Copyright © 2024 American Society of Hematology.