In vivo visualization and molecular targeting of the cardiac conduction system

Area of Science:

• Cardiovascular Biology
• Medical Imaging
• Molecular Cardiology

Background:

• Cardiac conduction system (CCS) injury is a significant complication during cardiac surgeries.
• The specialized cells of the CCS are difficult to distinguish from surrounding heart tissue, hindering targeted interventions.

Purpose of the Study:

• To engineer novel tools for in vivo visualization and potential therapeutic targeting of the cardiac conduction system.
• To identify new molecular targets for precise manipulation of CCS subcomponents.

Main Methods:

• Development of antibody-dye conjugates for in vivo optical imaging of the CCS in mice.
• Generation of a fully human monoclonal Fab fragment for CCS targeting.
• Single-cell RNA sequencing and differential gene expression analysis of the murine CCS.

Main Results:

• Engineered antibody-dye conjugates enabled sensitive, specific, and high-resolution in vivo imaging of the CCS without adverse effects.
• A fully human monoclonal Fab demonstrated high specificity for the CCS and potential for targeted therapeutic delivery.
• Identification and validation of novel cell surface markers for molecularly targeting distinct CCS subcomponents.

Conclusions:

• Novel antibody-dye conjugates and monoclonal antibodies provide powerful tools for in vivo CCS visualization and targeted therapy.
• These findings pave the way for improved strategies in cardiothoracic surgery, cardiac imaging, and arrhythmia management.
• The identified markers offer new avenues for developing precise treatments for life-threatening arrhythmias originating from specific CCS regions.