PBAE-Based Pulmonary siRNA Delivery to T-Cells: A Potential Approach for Asthma Therapy

Introduction: Asthma is a heterogeneous disease with distinct phenotypes driven by cytokine-based inflammatory pathways, particularly in allergic asthma. Type 2 T helper (Th2) cells produce key cytokines such as IL-4, IL-5, and IL-13, and silencing their transcription factor GATA3 offers therapeutic potential.[1] However, effective delivery to T cells remains a challenge. [2] We addressed this by developing Transferrin (Tf)-conjugated polybeta amino ester (PBAE) micelleplexes, which enhance siRNA stability and target activated T cells, presenting a promising approach for severe asthma therapy.