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基因治疗中的合成启动子:设计方法、特点及应用

Synthetic Promoters in Gene Therapy: Design Approaches, Features and Applications.

作者信息

Artemyev Valentin, Gubaeva Anna, Paremskaia Anastasiia Iu, Dzhioeva Amina A, Deviatkin Andrei, Feoktistova Sofya G, Mityaeva Olga, Volchkov Pavel Yu

机构信息

Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, 125315 Moscow, Russia.

Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia.

出版信息

Cells. 2024 Nov 27;13(23):1963. doi: 10.3390/cells13231963.

Abstract

Gene therapy is a promising approach to the treatment of various inherited diseases, but its development is complicated by a number of limitations of the natural promoters used. The currently used strong ubiquitous natural promoters do not allow for the specificity of expression, while natural tissue-specific promoters have lowactivity. These limitations of natural promoters can be addressed by creating new synthetic promoters that achieve high levels of tissue-specific target gene expression. This review discusses recent advances in the development of synthetic promoters that provide a more precise regulation of gene expression. Approaches to the design of synthetic promoters are reviewed, including manual design and bioinformatic methods using machine learning. Examples of successful applications of synthetic promoters in the therapy of hereditary diseases and cancer are presented, as well as prospects for their clinical use.

摘要

基因治疗是一种治疗各种遗传性疾病的有前景的方法,但其发展因所用天然启动子的一些局限性而变得复杂。目前使用的强组成型天然启动子无法实现表达的特异性,而天然组织特异性启动子活性较低。通过创建能够实现高水平组织特异性靶基因表达的新型合成启动子,可以解决天然启动子的这些局限性。本综述讨论了合成启动子开发的最新进展,这些合成启动子能对基因表达进行更精确的调控。综述了合成启动子的设计方法,包括人工设计和使用机器学习的生物信息学方法。介绍了合成启动子在遗传性疾病和癌症治疗中的成功应用实例,以及它们的临床应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f74/11640742/bdfc5939984f/cells-13-01963-g001.jpg

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