Noor Momin, PhD

Atrial fibrillation (Afib) affects nearly 1 in 10 elderly. Several factors cause Afib, but new insights reveal the immune system, specifically cytokines secreted by macrophages, plays a causal role. Therapies based on small interfering RNA (siRNA) offer a way to silence the expression of these cytokines in macrophages. However, only when targeted to specific cells and tissues, can siRNA be safely and effectively harnessed. In this project, we aim to address the challenge of cell-specific siRNA delivery by engineering antibody-siRNA conjugates (ARC). Thus far, using a “bedside-to-bench” approach, we have designed a first-generation ARC therapy and validated that it alleviates Afib in a clinically relevant mouse model. This promising molecule and ARCs as a modality now warrant investigation in the human context. In this project, we propose to 1) test, 2) engineer and 3) optimize personalized ARC treatments for Afib, thus enabling their rapid clinical translation.