作者
William R Goodyer, Benjamin M Beyersdorf, Lauren Duan, Nynke S van den Berg, Sruthi Mantri, Francisco X Galdos, Nazan Puluca, Jan W Buikema, Soah Lee, Darren Salmi, Elise R Robinson, Stephan Rogalla, Dillon P Cogan, Chaitan Khosla, Eben L Rosenthal, Sean M Wu
发表日期
2022/10/17
期刊
The Journal of Clinical Investigation
卷号
132
期号
20
出版商
American Society for Clinical Investigation
简介
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 …
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WR Goodyer, BM Beyersdorf, L Duan… - The Journal of Clinical Investigation, 2022