Bora Jutishna, Dey Ankita, Lyngdoh Antonia R, Dhasmana Archna, Ranjan Anuj, Kishore Shristi, Rustagi Sarvesh, Tuli Hardeep Singh, Chauhan Abhishek, Rath Prangya, Malik Sumira
Amity Institute of Biotechnology, Amity University Jharkhand, Ranchi, 834001, India.
Department of Biochemistry, North Eastern Hill University, Shillong, Meghalaya, 793022, India.
Naunyn Schmiedebergs Arch Pharmacol. 2023 Dec;396(12):3459-3481. doi: 10.1007/s00210-023-02631-1. Epub 2023 Jul 31.
Diabetes mellitus (D.M.) is a common metabolic disorder caused mainly by combining two primary factors, which are (1) defects in insulin production by the pancreatic β-cells and (2) responsiveness of insulin-sensitive tissues towards insulin. Despite the rapid advancement in medicine to suppress elevated blood glucose levels (hyperglycemia) and insulin resistance associated with this hazard, a demand has undoubtedly emerged to find more effective and curative dimensions in therapeutic approaches against D.M. The administration of diabetes treatment that emphasizes insulin production and sensitivity may result in unfavorable side effects, reduced adherence, and potential treatment ineffectiveness. Recent progressions in genome editing technologies, for instance, in zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR-Cas)-associated nucleases, have greatly influenced the gene editing technology from concepts to clinical practices. Improvements in genome editing technologies have also opened up the possibility to target and modify specific genome sequences in a cell directly. CRISPR/Cas9 has proven effective in utilizing ex vivo gene editing in embryonic stem cells and stem cells derived from patients. This application has facilitated the exploration of pancreatic beta-cell development and function. Furthermore, CRISPR/Cas9 enables the creation of innovative animal models for diabetes and assesses the effectiveness of different therapeutic strategies in treating the condition. We, therefore, present a critical review of the therapeutic approaches of the genome editing tool CRISPR-Cas9 in treating D.M., discussing the challenges and limitations of implementing this technology.
糖尿病（D.M.）是一种常见的代谢紊乱疾病，主要由两个主要因素共同作用引起，即（1）胰腺β细胞胰岛素分泌缺陷和（2）胰岛素敏感组织对胰岛素的反应性。尽管医学在抑制血糖水平升高（高血糖症）以及与此相关的胰岛素抵抗方面取得了快速进展，但毫无疑问，人们已经开始寻求在糖尿病治疗方法中找到更有效和更具治愈性的途径。强调胰岛素分泌和敏感性的糖尿病治疗方法可能会导致不良副作用、依从性降低以及潜在的治疗无效。例如，基因组编辑技术的最新进展，如锌指核酸酶、转录激活样效应物核酸酶和成簇规律间隔短回文重复序列（CRISPR-Cas）相关核酸酶，极大地推动了基因编辑技术从概念到临床实践的发展。基因组编辑技术的改进也为直接在细胞中靶向和修饰特定基因组序列开辟了可能性。CRISPR/Cas9已被证明在胚胎干细胞和患者来源的干细胞中利用体外基因编辑是有效的。这种应用促进了对胰腺β细胞发育和功能的探索。此外，CRISPR/Cas9能够创建用于糖尿病的创新动物模型，并评估不同治疗策略治疗该疾病的有效性。因此，我们对基因组编辑工具CRISPR-Cas9治疗糖尿病的治疗方法进行了批判性综述，讨论了实施该技术的挑战和局限性。
