Department of Pharmacology and Experimental Therapeutics, University of Toledo, Toledo, OH, 43614, USA.
Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, 43614, USA.
Gene Ther. 2023 Feb;30(1-2):1-7. doi: 10.1038/s41434-021-00304-3. Epub 2021 Nov 10.
Intracerebral hemorrhage (ICH) is a life-threatening condition with a high mortality rate. For survivors, quality of life is determined by primary and secondary phases of injury. The prospects for injury repair and recovery after ICH are highly dependent on the extent of secondary injury. Currently, no effective treatments are available to prevent secondary injury or its long-term effects. One promising strategy that has recently garnered attention is gene therapy, in particular, small interfering RNAs (siRNA), which silence specific genes responsible for destructive effects after hemorrhage. Gene therapy as a potential treatment for ICH is being actively researched in animal studies. However, there are many barriers to the systemic delivery of siRNA-based therapy, as the use of naked siRNA has limitations. Recently, the Food and Drug Administration approved two siRNA-based therapies, and several are undergoing Phase 3 clinical trials. In this review, we describe the advancements in siRNA-based gene therapy for ICH and also summarize its advantages and disadvantages.
脑出血 (ICH) 是一种危及生命的疾病,死亡率很高。对于幸存者来说,生活质量取决于损伤的原发期和继发期。ICH 后损伤修复和恢复的前景在很大程度上取决于继发损伤的程度。目前,尚无有效的治疗方法可预防继发损伤或其长期影响。最近受到关注的一种有前途的策略是基因治疗,特别是小干扰 RNA(siRNA),它可以沉默出血后导致破坏性影响的特定基因。基因治疗作为 ICH 的一种潜在治疗方法,正在动物研究中得到积极研究。然而,siRNA 为基础的治疗的全身递送存在许多障碍,因为裸 siRNA 的使用存在局限性。最近,美国食品和药物管理局批准了两种基于 siRNA 的疗法,还有几种正在进行 3 期临床试验。在这篇综述中,我们描述了基于 siRNA 的基因治疗在 ICH 中的进展,并总结了其优缺点。