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CRISPR/Cas 技术在疟原虫基因组编辑、诊断、治疗和疫苗开发方面的进展,以及疟蚊媒介的基因工程。

CRISPR/Cas advancements for genome editing, diagnosis, therapeutics, and vaccine development for Plasmodium parasites, and genetic engineering of Anopheles mosquito vector.

机构信息

Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran.

Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, Tehran, Iran.

出版信息

Infect Genet Evol. 2023 Apr;109:105419. doi: 10.1016/j.meegid.2023.105419. Epub 2023 Feb 24.

Abstract

Malaria as vector-borne disease remains important health concern with over 200 million cases globally. Novel antimalarial medicines and more effective vaccines must be developed to eliminate and eradicate malaria. Appraisal of preceding genome editing approaches confirmed the CRISPR/Cas nuclease system as a novel proficient genome editing system and a tool for species-specific diagnosis, and drug resistance researches for Plasmodium species, and gene drive to control Anopheles population. CRISPR/Cas technology, as a handy tool for genome editing can be justified for the production of transgenic malaria parasites like Plasmodium transgenic lines expressing Cas9, chimeric Plasmodium transgenic lines, knockdown and knockout transgenic parasites, and transgenic parasites expressing alternative alleles, and also mutant strains of Anopheles such as only male mosquito populations, generation of wingless mosquitoes, and creation of knock-out/ knock-in mutants. Though, the incorporation of traditional methods and novel molecular techniques could noticeably enhance the quality of results. The striking development of a CRISPR/Cas-based diagnostic kit that can specifically diagnose the Plasmodium species or drug resistance markers is highly required in malaria settings with affordable cost and high-speed detection. Furthermore, the advancement of genome modifications by CRISPR/Cas technologies resolves contemporary restrictions to culturing, maintaining, and analyzing these parasites, and the aptitude to investigate parasite genome functions opens up new vistas in the better understanding of pathogenesis.

摘要

疟疾作为一种媒介传播的疾病仍然是一个重要的健康关注点,全球有超过 2 亿例病例。为了消除和消灭疟疾,必须开发新的抗疟药物和更有效的疫苗。对先前的基因组编辑方法的评估证实,CRISPR/Cas 核酸酶系统是一种新型有效的基因组编辑系统,也是针对疟原虫物种进行特定诊断、药物耐药性研究以及控制疟蚊种群的基因驱动的工具。CRISPR/Cas 技术作为一种基因组编辑的便捷工具,可以用于生产转基因疟原虫,如表达 Cas9 的疟原虫转基因系、嵌合疟原虫转基因系、 knockdown 和 knockout 转基因寄生虫以及表达替代等位基因的转基因寄生虫,还可以用于生产如只有雄性蚊子种群的转基因疟蚊以及无翅蚊子的产生和敲除/敲入突变体。然而,结合传统方法和新型分子技术可以显著提高结果的质量。在疟疾环境中,非常需要一种基于 CRISPR/Cas 的诊断试剂盒,能够以可承受的成本和高速检测特异性诊断疟原虫物种或药物耐药性标记。此外,CRISPR/Cas 技术的基因组修饰的进步解决了培养、维持和分析这些寄生虫的当代限制,并且调查寄生虫基因组功能的能力为更好地理解发病机制开辟了新的前景。

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