转译拼接的治疗应用。
Therapeutic applications of trans-splicing.
机构信息
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
出版信息
Br Med Bull. 2020 Dec 15;136(1):4-20. doi: 10.1093/bmb/ldaa028.
Abstract
BACKGROUND
RNA trans-splicing joins exons from different pre-mRNA transcripts to generate a chimeric product. Trans-splicing can also occur at the protein level, with split inteins mediating the ligation of separate gene products to generate a mature protein.
SOURCES OF DATA
Comprehensive literature search of published research papers and reviews using Pubmed.
AREAS OF AGREEMENT
Trans-splicing techniques have been used to target a wide range of diseases in both in vitro and in vivo models, resulting in RNA, protein and functional correction.
AREAS OF CONTROVERSY
Off-target effects can lead to therapeutically undesirable consequences. In vivo efficacy is typically low, and delivery issues remain a challenge.
GROWING POINTS
Trans-splicing provides a promising avenue for developing novel therapeutic approaches. However, much more research needs to be done before developing towards preclinical studies.
AREAS TIMELY FOR DEVELOPING RESEARCH
Increasing trans-splicing efficacy and specificity by rational design, screening and competitive inhibition of endogenous cis-splicing.
摘要
背景
RNA 转剪接将来自不同前体 mRNA 转录本的外显子连接在一起，生成嵌合产物。转剪接也可以在蛋白质水平上发生，带有分裂整合酶的拼接体介导将不同基因产物连接在一起，以生成成熟蛋白质。
资料来源
使用 Pubmed 对已发表的研究论文和综述进行全面的文献检索。
共识领域
转剪接技术已被用于在体外和体内模型中靶向广泛的疾病，从而实现 RNA、蛋白质和功能校正。
争议领域
脱靶效应可能导致治疗上不理想的后果。体内疗效通常较低，并且仍存在递送问题。
发展点
转剪接为开发新的治疗方法提供了有前途的途径。然而，在开发进入临床前研究之前，还需要进行更多的研究。
值得研究的领域
通过合理设计、筛选和内源性顺式剪接的竞争性抑制来提高转剪接的效率和特异性。
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