Czerwińska Patrycja, Mazurek Sylwia, Kołodziejczak Iga, Wiznerowicz Maciej
Laboratory of Gene Therapy, Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland.
Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland.
Rep Pract Oncol Radiother. 2019 Mar-Apr;24(2):180-187. doi: 10.1016/j.rpor.2019.01.007. Epub 2019 Feb 18.
Induced pluripotent stem cells derived from normal somatic cells could be utilized to study tumorigenesis through overexpression of specific oncogenes, downregulation of tumor suppressors and dysregulation of other factors thought to promote tumorigenesis. Therefore, effective approaches that provide direct modifications of induced pluripotent stem cell genome are extremely needed. Emerging strategies are expected to provide the ability to more effectively introduce diverse genetic alterations, from as small as single-nucleotide modifications to whole gene amplification or deletion, all with a high degree of target specificity. To date, several techniques have been applied in stem cell studies to directly edit cell genome (ZFNs, TALENs or CRISPR/Cas9). In this review, we summarize specific gene delivery strategies that were applied to stem cell studies together with genome editing techniques, which enable a direct modification of endogenous DNA sequences in the context of cancer studies.
源自正常体细胞的诱导多能干细胞可用于通过特定癌基因的过表达、肿瘤抑制因子的下调以及其他被认为促进肿瘤发生的因子的失调来研究肿瘤发生。因此,极其需要能够直接修饰诱导多能干细胞基因组的有效方法。新兴策略有望提供更有效地引入各种基因改变的能力,从单个核苷酸修饰到全基因扩增或缺失,所有这些都具有高度的靶点特异性。迄今为止,已有几种技术应用于干细胞研究以直接编辑细胞基因组(锌指核酸酶、转录激活因子样效应物核酸酶或CRISPR/Cas9)。在本综述中,我们总结了应用于干细胞研究的特定基因传递策略以及基因组编辑技术,这些技术能够在癌症研究背景下直接修饰内源性DNA序列。