Genetically engineered transfusable platelets using mRNA lipid nanoparticles

Jerry Leung, Colton Strong, Katherine E. Badior, Madelaine Robertson, Xiaowu Wu, Michael A. Meledeo, Emma Kang, Manoj Paul, Yusuke Sato, Hideyoshi Harashima, Andrew P. Cap, Dana V. Devine, Eric Jan, Pieter R. Cullis, Christian J. Kastrup*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish
Article numbereadi0508
JournalScience Advances
Volume9
Issue number48
DOIs
StatePublished - Dec 2023
Externally publishedYes

Fingerprint

Dive into the research topics of 'Genetically engineered transfusable platelets using mRNA lipid nanoparticles'. Together they form a unique fingerprint.

Cite this