Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.
Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.
Curr Opin Pharmacol. 2021 Aug;59:140-148. doi: 10.1016/j.coph.2021.05.008. Epub 2021 Jul 1.
In light of recent advances in RNA splicing modulation as therapy for specific genetic diseases, there is great optimism that this approach can be applied to treatment of cancer as well. Dysregulation of alternative RNA splicing is a common aberration detected in many cancers and thus, provides an attractive target for therapeutics. Here, we present and compare two promising approaches that are currently being investigated to manipulate alternative splicing and their potential use in therapy. The first strategy makes use of splice-switching oligonucleotides, whereas the second strategy uses CRISPR (clustered regularly interspaced short palindromic repeat Cas (CRISPR-associated) technology. We will discuss both the challenges and limitations of these technologies and progress being made to implement splice-switching as a potential cancer therapy.
鉴于 RNA 剪接调控作为特定遗传疾病治疗方法的最新进展,人们非常乐观地认为,这种方法也可以应用于癌症的治疗。在许多癌症中都检测到了可变 RNA 剪接的失调,因此这为治疗提供了一个有吸引力的靶点。在这里,我们提出并比较了两种目前正在研究的有前途的方法,用于操纵可变剪接及其在治疗中的潜在用途。第一种策略利用了剪接转换寡核苷酸,而第二种策略则使用了 CRISPR(成簇的、规律间隔的短回文重复 CRISPR 相关)技术。我们将讨论这些技术的挑战和局限性,以及在实施剪接转换作为一种潜在的癌症治疗方法方面所取得的进展。