Inducible mouse line for cardiac NOX2 inhibition
This technology describes an inducible mouse line for the inhibition of cardiac-specific reactive oxygen species production.
Unmet Need: Selective targeting of reactive oxygen species to treat cardiac disease
Reactive oxygen species (ROS) can lead to oxidative damage and are linked to the pathophysiology of cardiovascular diseases. Current approaches to target ROS production in mice utilize antioxidants or global inhibitors, which can be nonselective and have off-target effects. Although there are genetic methods to spatiotemporally manipulate gene expression in specific tissues, there are currently no attempts to target cardiac ROS.
The Technology: Inducible inhibition of cardiac NOX2 in mice
This technology describes a mouse line with inducible cardiac expression of an endogenous NADPH oxidase 2 (NOX2) inhibitor, called negative regulator of reactive oxygen species (NRROS). This mouse line employs a Cre-lox recombination system to induce myocardial specific gene expression of NRROS. Using this approach, NOX2 activation can be blocked in the ventricular myocardium without disturbing baseline functions of NOX2 while also limiting global toxicity. This technology provides a tissue-specific approach to targeting ROS signaling in mice, with implications to further understand and treat cardiac diseases.
This mouse model has been validated, with successful inhibition of NOX2 protein production in the ventricular myocardium and protection against the early onset of ventricular tachycardia (VT) in high fat diet-fed mice.
Applications:
- Mouse model for studying reactive oxygen species (ROS) in heart disease
- Research tool for assessing altered myocardial ROS signaling
- Somatic gene therapy for cardiac diseases
- Precision medicine in cardiology
Advantages:
- Tissue-specific inducible transgene expression
- Physiologically relevant model to study ROS-associated heart diseases
- Inhibits cardiac NOX2 protein production, without impacting global NOX2
- Curbs the risks for toxicity in peripheral tissues
- Prevents oxidative damage associated with high fat diet-induced ventricular tachycardia
Lead Inventor:
Related Publications:
Tech Ventures Reference:
IR CU22219
Licensing Contact: Joan Martinez