| Literature DB >> 32865782 |
Tejal Aslesh1,2, Toshifumi Yokota3,4.
Abstract
The field of neuromuscular and neurodegenerative diseases has been revolutionized by the advent of genetics and molecular biology to evaluate the pathogenicity, thereby providing considerable insight to develop suitable therapies. With the successful translation of antisense oligonucleotides (AOs) from in vitro into animal models and clinical practice, modifications are being continuously made to the AOs to improve the pharmacokinetics and pharmacodynamics. In order to activate RNase H-mediated cleavage of the target mRNA, as well as to increase the binding affinity and specificity, gapmer AOs are designed to have a phosphorothioate (PS) backbone flanked with the modified AOs on both sides. Antisense-mediated knockdown of mutated huntingtin is a promising therapeutic approach for Huntington's disease (HD), a devastating disorder affecting the motor and cognitive abilities. This chapter focuses on the modified gapmer AOs for the treatment of HD.Entities:
Keywords: 2′-O-methoxyethyl (MOE); Eteplirsen (brand name Exondys 51); Gapmer; HTTRX (Alternative Names: HTT ASO; IONIS-HTTRx; ISIS-443139; ISIS-HTT Rx; RG 6042; RO7234292); Huntingtin (HTT); Nusinersen (brand name Spinraza); Short interfering RNA (siRNA); Trinucleotide repeat disorders; WVE-120101/WVE-120102; Zinc-finger proteins (ZFPs)
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Year: 2020 PMID： 32865782 DOI： 10.1007/978-1-0716-0771-8_4
Source DB: PubMed Journal: Methods Mol Biol ISSN： 1064-3745