Laboratory of Genomics & Bioinformatics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland.
Faculty of Life Sciences and Medicine, Guy's Campus, King's College London, London SE1 9RT, UK.
Int J Mol Sci. 2022 Jan 5;23(1):573. doi: 10.3390/ijms23010573.
Cancer is a devastating condition characterised by the uncontrolled division of cells with many forms remaining resistant to current treatment. A hallmark of cancer is the gradual accumulation of somatic mutations which drive tumorigenesis in cancerous cells, creating a mutation landscape distinctive to a cancer type, an individual patient or even a single tumour lesion. Gene editing with CRISPR/Cas9-based tools now enables the precise and permanent targeting of mutations and offers an opportunity to harness this technology to target oncogenic mutations. However, the development of safe and effective gene editing therapies for cancer relies on careful design to spare normal cells and avoid introducing other mutations. This article aims to describe recent advancements in cancer-selective treatments based on the CRISPR/Cas9 system, especially focusing on strategies for targeted delivery of the CRISPR/Cas9 machinery to affected cells, controlling Cas9 expression in tissues of interest and disrupting cancer-specific genes to result in selective death of malignant cells.
癌症是一种破坏性疾病，其特征是细胞的失控分裂，目前许多形式的癌症仍然对治疗有耐药性。癌症的一个标志是体细胞突变的逐渐积累，这些突变驱动了癌细胞的肿瘤发生，为特定癌症类型、个体患者甚至单个肿瘤病变创造了独特的突变景观。基于 CRISPR/Cas9 的基因编辑工具现在可以精确和永久地靶向突变，并为利用这项技术靶向致癌突变提供了机会。然而，开发安全有效的癌症基因编辑疗法依赖于精心设计以保护正常细胞并避免引入其他突变。本文旨在描述基于 CRISPR/Cas9 系统的癌症选择性治疗的最新进展，特别是专注于将 CRISPR/Cas9 机制靶向递送至受影响细胞的策略，控制感兴趣组织中 Cas9 的表达以及破坏癌症特异性基因以导致恶性细胞选择性死亡。
