van de Vrugt Henri J, Cornel Martina C, Wolthuis Rob M F
Amsterdam Cancer Center, Amsterdam UMC, afd. Klinische Genetica, sectie Oncogenetica, Amsterdam.
Contact: H.J. van de Vrugt (
Ned Tijdschr Geneeskd. 2018 Jun 29;162:D2461.
CRISPR/Cas gene editing makes it much easier to make targeted changes in the DNA of human cells than other forms of gene therapy. This revolutionary technology offers spectacular opportunities to study gene functions; the clinical consequences of gene variations in patients can be determined much faster. The efficacy and accuracy of CRISPR/Cas is so impressive that a breakthrough to therapeutic applications is approaching fast. CRISPR/Cas is already being used in immunotherapy against cancer, and trials for monogenetic blood disorders, such as beta-thalassemia, have been scheduled. However, broad clinical implementation of CRISPR/Cas is not feasible yet, due to off-target DNA changes that may occur as a by-product. Particularly in case of in-vivo applications there are therapeutic challenges. For gene editing in human embryos, technical shortcomings and open ethical issues need to be addressed. Gene-editing therapy for serious disorders with transplantable cell types, and therefore the option of verification of "CRISPRed" cells, is seen as a possible first application within the regular healthcare system.
与其他形式的基因疗法相比，CRISPR/Cas基因编辑技术使对人类细胞DNA进行靶向改变变得更加容易。这项革命性技术为研究基因功能提供了绝佳机遇；能够更快地确定患者基因变异的临床后果。CRISPR/Cas的有效性和准确性令人印象深刻，以至于距离其在治疗应用上取得突破已为期不远。CRISPR/Cas已被用于癌症免疫治疗，针对单基因血液疾病（如β地中海贫血）的试验也已安排就绪。然而，由于可能作为副产物出现的脱靶DNA改变，CRISPR/Cas在临床上的广泛应用目前尚不可行。特别是在体内应用的情况下，存在治疗方面的挑战。对于人类胚胎的基因编辑，技术缺陷和开放的伦理问题需要得到解决。针对具有可移植细胞类型的严重疾病的基因编辑疗法，以及因此对“经CRISPR编辑”细胞进行验证的选择，被视为常规医疗保健系统内可能的首个应用。
