University of KwaZulu-Natal, College of Health Sciences, Department of Medical Microbiology, Durban, KwaZulu-Natal, South Africa.
South African Medical Research Council (SAMRC), Division of Research Capacity Development, Cape Town, Western Cape, South Africa.
Rev Soc Bras Med Trop. 2022 Aug 12;55:e0131. doi: 10.1590/0037-8682-0131-2022. eCollection 2022.
Schistosomiasis is a neglected acute and chronic tropical disease caused by intestinal (Schistosoma mansoni and Schistosoma japonicum) and urogenital (Schistosoma haematobium) helminth parasites (blood flukes or digenetic trematodes). It afflicts over 250 million people worldwide, the majority of whom reside in impoverished tropical and subtropical regions in sub-Saharan Africa. Schistosomiasis is the second most common devastating parasitic disease in the world after malaria and causes over 200,000 deaths annually. Currently, there is no effective and approved vaccine available for human use, and treatment strongly relies on praziquantel drug therapy, which is ineffective in killing immature larval schistosomula stages and eggs already lodged in the tissues. The Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9)-mediated gene editing tool is used to deactivate a gene of interest to scrutinize its role in health and disease, and to identify genes for vaccine and drug targeting. The present review aims to summarize the major findings from the current literature reporting the usage of CRISPR/Cas9-mediated gene editing to inactivate genes in S. mansoni (acetylcholinesterase (AChE), T2 ribonuclease omega-1 (ω1), sulfotransferase oxamniquine resistance protein (SULT-OR), and α-N-acetylgalactosaminidase (SmNAGAL)), and freshwater gastropod snails, Biomphalaria glabrata (allograft inflammatory factor (BgAIF)), an obligatory component of the life cycle of S. mansoni, to identify their roles in the pathogenesis of schistosomiasis, and to highlight the importance of such studies in identifying and developing drugs and vaccines with high therapeutic efficacy.
血吸虫病是一种被忽视的急性和慢性热带病,由肠道(曼氏血吸虫和日本血吸虫)和泌尿生殖系统(埃及血吸虫)的寄生虫(血吸 虫或双腔吸虫)引起。它影响了全球超过 2.5 亿人,其中大多数人生活在撒哈拉以南非洲的贫困热带和亚热带地区。血吸虫病是世界上仅次于疟疾的第二大常见破坏性寄生虫病,每年导致超过 20 万人死亡。目前,尚无有效的人类可用疫苗,治疗主要依赖于吡喹酮药物治疗,但该药物在杀死未成熟的幼虫蚴和已经在组织中定居的卵方面效果不佳。簇状规则间隔短回文重复序列/CRISPR 相关蛋白 9 (CRISPR/Cas9)介导的基因编辑工具用于失活感兴趣的基因,以研究其在健康和疾病中的作用,并鉴定用于疫苗和药物靶向的基因。本综述旨在总结当前文献中报告的使用 CRISPR/Cas9 介导的基因编辑来失活曼氏血吸虫(乙酰胆碱酯酶 (AChE)、T2 核糖核酸酶 ω1 (ω1)、磺基转移酶奥沙米喹抗性蛋白 (SULT-OR) 和 α-N-乙酰半乳糖胺酶 (SmNAGAL))和淡水腹足纲蜗牛,光滑萝卜螺 (BgAIF)(同种异体炎症因子)基因的主要发现,以确定它们在血吸虫病发病机制中的作用,并强调此类研究在鉴定和开发具有高治疗疗效的药物和疫苗方面的重要性。