Universal gene editing strategy for cardiac arrhythmia

This technology is a treatment for cardiac arrhythmias that utilizes gene editing in the phosphorylation sites of the Rad gene.

Unmet Need: Precision therapies for cardiac arrhythmias

Calcium ion channels have various effects on cardiac function and muscle contraction. Dysregulation of these channels, potentially due to genetic defects, can cause or exacerbate cardiac arrhythmia syndromes. Current treatments for cardiac arrhythmias include medications, implantable devices, and surgical procedures designed to regulate heart rhythm. However, anti-arrhythmic drugs like beta-blockers are non-specific, resulting in many off-target effects.

The Technology:

This technology is a potential universal therapy for cardiac arrhythmias that leverages gene editing of phosphorylation sites in the Rad gene to prevent its phosphorylation. Inhibition of Rad phosphorylation has been shown to induce an anti-arrhythmic effect through suppressing the adrenergic regulation of the calcium current. This approach is more specific than current anti-arrhythmic drugs, reducing off-target side effects.

Applications:

• Treatment for cardiac arrhythmias
• Treatment for diseases induced by adrenergic agonists
• Research model for studying Rad phosphorylation
• Research model for studying the relationship between Rad and calcium current regulation
• Method for modulating adrenergic regulation of calcium current and calcium influx
• Platform for gene editing and drug screening

Advantages:

• Specific inhibition of adrenergic signaling
• Reduced side effects
• Permanent genetic cure rather than continuous medication
• Generic gene editing rather than a patient-specific edit

Lead Inventor:

Steven Marx, M.D.

Related Publications:

• Liu G, Papa A, Katchman AN, Zakharov SI, Roybal D, Hennessey JA, Kushner J, Yang L, Chen BX, Kushnir A, Dangas K, Gygi SP, Pitt GS, Colecraft HM, Ben-Johny M, Kalocsay M, Marx SO. “Mechanism of adrenergic CaV1.2 stimulation revealed by proximity proteomics.” Nature. 2020 Jan; 577(7792): 695-700.

• Papa A, Zakharov SI, Katchman AN, Kushner JS, Chen BX, Yang L, Liu G, Jimenez AS, Eisert RJ, Bradshaw GA, Dun W, Ali SR, Rodriques A, Zhou K, Topkara V, Yang M, Morrow JP, Tsai EJ, Karlin A, Wan E, Kalocsay M, Pitt GS, Colecraft HM, Ben-Johny M, Marx SO. “Rad regulation of CaV1.2 channels controls cardiac fight-or-flight response.” Nat Cardiovasc Res. 2022 Nov; 1(11): 1022-1038.

Tech Ventures Reference:

• IR CU24243

• Licensing Contact: Joan Martinez