David W Wolfson, Nam Kyun Kim, Ki Hong Lee, Jared P Beyersdorf, Jonathan J Langberg, Natasha Fernandez, Dahim Choi, Nadine Zureick, Tae Yun Kim, Seongho Bae, Jin-Mo Gu, Jonathan L Kirschman, Jinqi Fan, Christina Y Sheng, Danielle Gottlieb Sen, Bret Mettler, Jung Hoon Sung, Young-Sup Yoon, Sung-Jin Park, Philip J Santangelo, Hee Cheol Cho
The adenovirus-mediated somatic transfer of the embryonic T-box transcription factor 18 (TBX18) gene can convert chamber cardiomyocytes into induced pacemaker cells. However, the translation of therapeutic TBX18-induced cardiac pacing faces safety challenges. Here we show that the myocardial expression of synthetic TBX18 mRNA in animals generates de novo pacing and limits innate and inflammatory immune responses. In rats, intramyocardially injected mRNA remained localized, whereas direct myocardial injection of an adenovirus carrying a reporter gene resulted in diffuse expression and in substantial spillover to the liver, spleen and lungs...
May 2, 2024: Nature Biomedical Engineering