Aartsma-Rus Annemieke
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Methods Mol Biol. 2012;867:117-29. doi: 10.1007/978-1-61779-767-5_8.
Antisense-mediated exon skipping is an attractive tool to study gene function as well as a promising therapeutic application for a number of diseases. In order for antisense oligonucleotides (AONs) to induce effective exon skipping during pre-mRNA splicing, they have to fulfill certain criteria. These include resistance against endo- and exonucleases and RNase H-induced cleavage and suitable thermodynamic properties. Furthermore, the AON-target sequence needs to be accessible and should contain sequence motives that are essential for proper inclusion of the exon into the mRNA. For most genes, only a few AONs have been designed, with the exception of the DMD gene, for which over 400 AONs targeting the majority of DMD exons have been reported. This allows retrospective analysis of effective and ineffective AONs to obtain guidelines to optimize future AON design.
反义介导的外显子跳跃是一种用于研究基因功能的有吸引力的工具，也是治疗多种疾病的一种有前景的治疗方法。为了使反义寡核苷酸（AONs）在mRNA前体剪接过程中诱导有效的外显子跳跃，它们必须满足某些标准。这些标准包括对内切酶和外切酶以及RNase H诱导的切割具有抗性，以及合适的热力学性质。此外，AON靶向序列需要易于接近，并且应包含将外显子正确纳入mRNA所必需的序列基序。对于大多数基因，仅设计了少数AONs，但DMD基因除外，针对该基因已报道了400多种靶向大多数DMD外显子的AONs。这使得可以对有效和无效的AONs进行回顾性分析，以获得优化未来AON设计的指导原则。
