Genetically engineered transfusable platelets using mRNA lipid nanoparticles.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
medline:
4
12
2023
pubmed:
1
12
2023
entrez:
1
12
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 38039367
doi: 10.1126/sciadv.adi0508
pmc: PMC10691771
doi:
Substances chimiques
Lipid Nanoparticles
0
RNA, Messenger
0
Hemostatics
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eadi0508Subventions
Organisme : U.S. Department of Defense Investigator-Initiated Research Award
ID : W81XWH202004
Organisme : Frederick Banting and Charles Best Doctoral Award
ID : 6552
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