Optimization of Strategy for Modified mRNA Inducing Cardiac-Specific Expression in Mice.
J Cardiovasc Transl Res
; 16(5): 1078-1084, 2023 Oct.
Article
em En
| MEDLINE
| ID: mdl-37155138
ABSTRACT
Lipid nanoparticle (LNP)-coated-modified RNA(modRNA) has been developed for enhancing the stability of modRNA, but it tends to accumulate in liver. The current study aimed to optimize strategy for increasing cardiac expression efficiency of modRNA. We synthesized Luciferase (Luc)-modRNA, and also developed 122Luc modRNA, a liver silencing Luc modRNA. Intramyocardial injection of naked Luc modRNA induced high bioluminescence signal in heart, but very low in other organs including liver. Luc modRNA-LNP injection showed the signal was increased by 5 folds in the heart and by 15,000 folds in the liver, compared to naked Luc modRNA group. In comparison with Luc modRNA-LNP group, the liver signal was decreased to 0.17%, while cardiac signal showed a slight drop by intramyocardial injection of 122Luc-modRNA-LNP. Our data revealed that intramyocardial injection of naked modRNA could effectively induced cardiac-specific expression. For cardiac delivery of Luc modRNA-LNP, 122modRNA-LNP enhances specificity of cardiac expression by abolishing liver signal.
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Base de dados:
MEDLINE
Assunto principal:
Técnicas de Transferência de Genes
/
Nanopartículas
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article