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

Publication ,  Journal Article
Nguyen, HX; Wu, T; Needs, D; Zhang, H; Perelli, RM; DeLuca, S; Yang, R; Pan, M; Landstrom, AP; Henriquez, C; Bursac, N
Published in: Nature communications
February 2022

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 (BacNav) 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 BacNav significantly reduces occurrence of conduction block and reentrant arrhythmias in fibrotic cardiac cultures. Moreover, functional BacNav channels are stably expressed in healthy mouse hearts six weeks following intravenous injection of self-complementary adeno-associated virus (scAAV) without causing any adverse effects on cardiac electrophysiology. The large diversity of prokaryotic sodium channels and experimental-computational platform reported in this study should facilitate the development and evaluation of BacNav-based gene therapies for cardiac conduction disorders.

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Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

February 2022

Volume

13

Issue

1

Start / End Page

620

Related Subject Headings

  • Voltage-Gated Sodium Channels
  • Rats, Sprague-Dawley
  • Rats
  • NAV1.5 Voltage-Gated Sodium Channel
  • Myocytes, Cardiac
  • Muscle Proteins
  • Mice
  • Male
  • Humans
  • HEK293 Cells
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nguyen, H. X., Wu, T., Needs, D., Zhang, H., Perelli, R. M., DeLuca, S., … Bursac, N. (2022). Engineered bacterial voltage-gated sodium channel platform for cardiac gene therapy. Nature Communications, 13(1), 620. https://doi.org/10.1038/s41467-022-28251-6
Nguyen, Hung X., Tianyu Wu, Daniel Needs, Hengtao Zhang, Robin M. Perelli, Sophia DeLuca, Rachel Yang, et al. “Engineered bacterial voltage-gated sodium channel platform for cardiac gene therapy.Nature Communications 13, no. 1 (February 2022): 620. https://doi.org/10.1038/s41467-022-28251-6.
Nguyen HX, Wu T, Needs D, Zhang H, Perelli RM, DeLuca S, et al. Engineered bacterial voltage-gated sodium channel platform for cardiac gene therapy. Nature communications. 2022 Feb;13(1):620.
Nguyen, Hung X., et al. “Engineered bacterial voltage-gated sodium channel platform for cardiac gene therapy.Nature Communications, vol. 13, no. 1, Feb. 2022, p. 620. Epmc, doi:10.1038/s41467-022-28251-6.
Nguyen HX, Wu T, Needs D, Zhang H, Perelli RM, DeLuca S, Yang R, Pan M, Landstrom AP, Henriquez C, Bursac N. Engineered bacterial voltage-gated sodium channel platform for cardiac gene therapy. Nature communications. 2022 Feb;13(1):620.

Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

February 2022

Volume

13

Issue

1

Start / End Page

620

Related Subject Headings

  • Voltage-Gated Sodium Channels
  • Rats, Sprague-Dawley
  • Rats
  • NAV1.5 Voltage-Gated Sodium Channel
  • Myocytes, Cardiac
  • Muscle Proteins
  • Mice
  • Male
  • Humans
  • HEK293 Cells