Oligonucleotide compositions and methods thereof

The present disclosure provides, among other things, oligonucleotides, compositions, and methods for the prevention and/or treatment of various conditions, disorders, or diseases. In some embodiments, provided techniques comprise nucleobase modifications, sugar modifications, inter-nucleotide linkage modifications, and/or patterns thereof, and have improved properties, activity, and/or selectivity. In some embodiments, the provided techniques target MAPT. In some embodiments, the disclosure provides MAPT oligonucleotides, compositions, and methods for the prevention and/or treatment of a condition, disorder, or disease associated with MAPT, such as Alzheimer's disease (AD) or frontotemporal dementia (FTD). 除其他事项外，本披露提供了用于预防和/或治疗各种病症、障碍或疾病的寡核苷酸、组合物和方法。在一些实施例中，提供的技术包含核碱基修饰、糖修饰、核苷酸间键联修饰和/或其模式，并且具有改善的特性、活性和/或选择性。在一些实施例中，所提供的技术靶向MAPT。在一些实施例中，本披露提供了用于预防和/或治疗与MAPT相关的病症、障碍或疾病，例如阿尔茨海默病(AD)或额颞叶痴呆(FTD)的MAPT寡核苷酸、组合物和方法。