CRISPR-Cas:从细菌免疫到精确基因组工程

IF 0.9 Q4 GENETICS & HEREDITY
Sidra Abbas , Ayesha Saeed , Monaza Bibi , Shaghufta Perveen , Nosheen Masood
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引用次数: 0

摘要

CRISPR-Cas系统是一种细菌的适应性免疫策略,已迅速转变为现代基因组工程的基石,在医学、农业和生物技术方面有着广泛的应用。本文综述了其分子基础,并强调了其不断扩大的功能范围,包括在免疫、DNA修复和转录调节中的作用。CRISPR技术已成为应对重大全球卫生挑战的有力工具,能够对耐药寄生虫(如疟原虫和克氏锥虫)进行精确的基因组修饰,并提供了对抗艾滋病毒和乙型肝炎等持续性病毒感染的有希望的战略。然而,挑战依然存在,特别是脱靶效应的风险,这突出表明需要改进精密工具和创新的递送方法。最近的进展正在通过下一代方法解决这些限制,例如工程病毒样颗粒、DNA纳米结构和合成外泌体正在提高递送效率和靶向特异性,而生物反应性水凝胶则提供受控的、特定位点的编辑成分释放。与此同时,较新的工具,如主要编辑系统和Cas12变体,正在实现高度精确的双链无断裂修饰,并具有扩展的靶向能力。这些进展为基因组编辑指明了一个更安全、适应性更强的未来。CRISPR的变革性影响将取决于改进递送策略、提高精确度以及建立健全的伦理和监管框架。随着应用的扩大,特别是在生殖细胞编辑方面,围绕代际同意、人类增强和潜在的优生滥用的伦理问题变得越来越紧迫。非治疗性基因改造的可能性进一步提高了公平获取和强有力的全球监督的必要性,以避免加深健康差距。CRISPR的未来在于协调科学创新与社会责任——确保进步既具有影响力又有道德基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CRISPR-Cas: From bacterial immunity to precision genome engineering
The CRISPR-Cas system is an adaptive immune strategy in bacteria that has rapidly transformed into a cornerstone of modern genome engineering with broad applications in medicine, agriculture, and biotechnology. This review explores its molecular foundations and highlights its expanding functional scope, including roles in immunity, DNA repair, and transcriptional regulation. CRISPR technology has emerged as a powerful tool in addressing major global health challenges, enabling precise genome modifications in drug-resistant parasites such as Plasmodium and Trypanosoma cruzi, as well as offering promising strategies against persistent viral infections like HIV and hepatitis B. However, challenges remain, particularly the risk of off-target effects, which underscores the need for refined precision tools and innovative delivery methods. Recent advances are addressing these limitations through next-generation approaches such as engineered virus-like particles, DNA nanostructures, and synthetic exosomes are improving delivery efficiency and targeting specificity, while bioresponsive hydrogels offer controlled, site-specific release of editing components. At the same time, newer tools like prime editing systems and Cas12 variants are achieving highly accurate, double-strand break–free modifications with expanded targeting capacity. These advances point toward a safer, more adaptable future for genome editing. CRISPR's transformative impact will depend on improving delivery strategies, enhancing precision, and establishing robust ethical and regulatory frameworks. As applications expand, particularly in germline editing, ethical concerns surrounding intergenerational consent, human enhancement, and potential eugenic misuse become increasingly pressing. The possibility of non-therapeutic genetic modification further elevates the need for equitable access and strong global oversight to avoid deepening health disparities. The future of CRISPR lies in harmonizing scientific innovation with societal responsibility—ensuring that progress is both impactful and ethically grounded.
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来源期刊
Gene Reports
Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
7.70%
发文量
246
审稿时长
49 days
期刊介绍: Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.
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