Belete Tafere Mulaw
Department of Pharmacology, College of Medicine and Health Sciences, University of Gondar, Gondar, Amhara Region, Ethiopia.
Biologics. 2021 Mar 18;15:67-77. doi: 10.2147/BTT.S302095. eCollection 2021.
Gene therapy is the administration of foreign genomic material into the host tissue to modify the expression of a gene product or to change the biological properties of cells for therapeutic use. Initially, the major objective of gene therapy was to manage genetic diseases, but now different disorders with several patterns of acquired and inherited disorders are targets of gene therapy. Over three decades, the advancement of Genome engineering technologies facilitated gene therapy for the prevention and management of intractable diseases. Researchers are advancing with cautious optimism that safe and effective treatment will give to patients with single-gene disorders and complex acquired disorders. To date, over 3000 genes associates with disease-causing mutations, and about 2600 gene therapy trials are undergoing for the management of various disorders. This review summarizes the principles of genome-editing approaches, such as zinc finger nucleases, transcription activator-like effector nucleases, meganucleases, and the CRISPR/Cas9 system with the underlying mechanisms. This review also explains the types of gene delivery systems as viral [adenoviral, adeno association, herpes simplex virus] and nonviral delivery systems (physical: DNA bombardment, electroporation) and (chemical: Cationic lipids, cationic polymers). Finally, this review summarizes gene therapy medicines approved to treat cancer in detail, including names, indications, vectors, and mode of gene therapy. Gene therapy becomes an alternative to an existing management for different diseases. Therefore, gene products with safe vectors and better biotechnologies play a significant role in the prophylaxis and management of various disorders in the future.
基因治疗是将外源基因组物质导入宿主组织，以改变基因产物的表达或改变细胞的生物学特性用于治疗。最初，基因治疗的主要目标是治疗遗传疾病，但现在多种获得性和遗传性疾病模式的不同病症都是基因治疗的靶点。在过去三十多年里，基因组工程技术的进步推动了基因治疗在难治性疾病预防和治疗方面的发展。研究人员正带着谨慎的乐观态度前进，认为安全有效的治疗将提供给患有单基因疾病和复杂获得性疾病的患者。迄今为止，超过3000个基因与致病突变相关，约2600项基因治疗试验正在进行以治疗各种病症。本综述总结了基因组编辑方法的原理，如锌指核酸酶、转录激活样效应物核酸酶、大范围核酸酶以及具有潜在机制的CRISPR/Cas9系统。本综述还解释了基因递送系统的类型，如病毒递送系统（腺病毒、腺相关病毒、单纯疱疹病毒）和非病毒递送系统（物理方法：DNA轰击、电穿孔）以及（化学方法：阳离子脂质、阳离子聚合物）。最后，本综述详细总结了已批准用于治疗癌症的基因治疗药物，包括名称、适应症、载体和基因治疗方式。基因治疗成为现有各种疾病治疗方法的一种替代选择。因此，具有安全载体和更好生物技术的基因产物在未来各种病症的预防和治疗中将发挥重要作用。
