Chicken cardiac troponin T (cTnT) promoter

Truncated ~418 bp (-375 to +43) chicken cardiac troponin T (cTnT) promoter fragment that restricts transgene expression almost exclusively to cardiomyocytes. Standard compact cardiac-specific promoter for systemic AAV delivery, giving strong myocardial expression with minimal expression in skeletal muscle or other tissues.

Length: 413 bp

Strength: moderate

Tissue: Cardiomyocytes; minimal skeletal muscle or non-muscle expression

Expression: constitutive

Origin: Chicken cardiac troponin T gene, truncated 418 bp proximal promoter fragment

Characteristics

A further-truncated 418 bp (-375 to +43) chicken cTnT promoter gives almost exclusive and substantial GFP or luciferase expression in the myocardium of young mice following systemic AAV8 or AAV9 injection, with expression across the injected population following a Poisson distribution consistent with a random multiplicity-of-infection process. AAV9 combined with this promoter is markedly more efficient than AAV1, AAV2, or AAV6 for reaching cardiomyocytes via systemic delivery.

Applications: Cardiomyocyte-restricted transgene expression following systemic AAV8/AAV9 delivery, including cardioprotective transgene expression (e.g. extracellular superoxide dismutase) and cardiac-restricted CRISPR nuclease delivery.

Limitations: Substantially weaker than ubiquitous promoters such as CMV in absolute output, trading strength for cardiac restriction. Cardiac specificity and expression level are serotype-dependent - the promoter must be paired with a cardiotropic AAV serotype (AAV8 or AAV9) to achieve efficient myocardial transduction via systemic delivery.

Sequence

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References

  1. Prasad et al. (2010). Robust cardiomyocyte-specific gene expression following systemic injection of AAV: in vivo gene delivery follows a Poisson distribution. Gene Ther - Prasad 2010 cTnT AAV Poisson