Key result
Antibody-dye conjugate mCntn2-800 visualizes the murine cardiac conduction system with ~147% higher signal-to-background ratio.
Why the study?
Accidental injury to the cardiac conduction system is a major complication in cardiac surgeries because it is indistinguishable from surrounding heart muscle tissue.
Do targeted antibody-dye conjugates and monoclonal Fabs allow for in vivo visualization and modulation of the cardiac conduction system in mice?
Do targeted antibody-dye conjugates and monoclonal Fabs allow for in vivo visualization and modulation of the cardiac conduction system in mice?
Absolute Event Rate: 4.463% vs 1.81%
p-value: p=0.0001
The development of targeted antibody-dye conjugates and a human monoclonal Fab enables in vivo visualization and molecular modulation of the cardiac conduction system, offering potential for surgical guidance and targeted arrhythmia therapies.
Hypothesis-generating for intraoperative conduction system imaging; requires human validation before clinical translation.
Accidental injury to the cardiac conduction system (CCS), a network of specialized cells embedded within the heart and indistinguishable from the surrounding heart muscle tissue, is a major complication in cardiac surgeries. Here, we addressed this unmet need by engineering targeted antibody-dye conjugates directed against the CCS, allowing for the visualization of the CCS in vivo following a single intravenous injection in mice. These optical imaging tools showed high sensitivity, specificity, and resolution, with no adverse effects on CCS function. Further, with the goal of creating a viable prototype for human use, we generated a fully human monoclonal Fab that similarly targets the CCS with high specificity. We demonstrate that, when conjugated to an alternative cargo, this Fab can also be used to modulate CCS biology in vivo, providing a proof of principle for targeted cardiac therapeutics. Finally, in performing differential gene expression analyses of the entire murine CCS at single-cell resolution, we uncovered and validated a suite of additional cell surface markers that can be used to molecularly target the distinct subcomponents of the CCS, each prone to distinct life-threatening arrhythmias. These findings lay the foundation for translational approaches targeting the CCS for visualization and therapy in cardiothoracic surgery, cardiac imaging, and arrhythmia management.
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Goodyer et al. (2022) studied Cardiac conduction system visualization. mCntn2-800 vs. Control IgG-800 was evaluated on Signal to background ratio (SBR) for CCS localization (p=0.0001). The targeted antibody-dye conjugate mCntn2-800 enabled in vivo visualization of the cardiac conduction system in mice, demonstrating a significantly higher signal-to-background ratio than control.
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