[2PS-040]
우수논문발표상 응모자Enhancing Nucleus Delivery of ASO in SMA and AD Treatment
발표자이다혜 (서울대학교)
연구책임자이혁진 (서울대학교)
Abstract
Antisense oligonucleotides (ASOs) modulate gene expression through sequence-specific interactions with target RNAs; however, their therapeutic application is often limited by poor nuclear delivery, necessitating high dosing and raising safety concerns. In this study, a novel delivery approach that integrates steroid hormone receptor-mediated nuclear transport with optimized lipid nanoparticle (LNP) technology to improve ASO nuclear localization was developed. In cell-based assays, dexamethasone-conjugated ASOs targeting spinal muscular atrophy (SMA) and Alzheimer’s disease (AD) exhibited more than a 3-fold increase in splicing modulation efficiency compared with unconjugated counterparts. Collectively, this strategy establishes a versatile platform for low-dose, efficient, and precise ASO-based gene therapies.