Engineered bacterial voltage-gated sodium channel platform for cardiac gene therapy.

ABSTRACT: Therapies for cardiac arrhythmias could greatly benefit from approaches to enhance electrical excitability and action potential conduction in the heart by stably overexpressing mammalian voltage-gated sodium channels. However, the large size of these channels precludes their incorporation into therapeutic viral vectors. Here, we report a platform utilizing small-size, codon-optimized engineered prokaryotic sodium channels (BacNa_v) driven by muscle-specific promoters that significantly enhance excitability and conduction in rat and human cardiomyocytes in vitro and adult cardiac tissues from multiple species in silico. We also show that the expression of BacNa_v significantly reduces occurrence of conduction block and reentrant arrhythmias in fibrotic cardiac cultures.

SUBMITTER: Nguyen HX 

PROVIDER: S-EPMC8810800 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature