Enhancing Nucleus Delivery of ASO in SMA and AD Treatment
발표자
이다혜 (서울대학교)
연구책임자
이혁진 (서울대학교)
공동저자
이다혜 (서울대학교), 이혁진 (서울대학교)
초록
내용
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.