Go D E, Stottmann R W
Divisions of Human Genetics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Curr Mol Med. 2016;16(4):343-52. doi: 10.2174/1566524016666160316150847.
There has been prolonged and significant interest in manipulating the genome for a wide range of applications in biomedical research and medicine. An existing challenge in realizing this potential has been the inability to precisely edit specific DNA sequences. Past efforts to generate targeted double stranded DNA cleavage have fused DNA-targeting elements such as zinc fingers and DNA-binding proteins to endonucleases. However, these approaches are limited by both design complexity and inefficient, costineffective operation. The discovery of CRISPR/Cas9, a branch of the bacterial adaptive immune system, as a potential genomic editing tool holds the promise of facile targeted cleavage. Its novelty lies in its RNA-guided endonuclease activity, which enhances its efficiency, scalability, and ease of use. The only necessary components are a Cas9 endonuclease protein and an RNA molecule tailored to the gene of interest. This lowbarrier of adoption has facilitated a plethora of advances in just the past three years since its discovery. In this review, we will discuss the impact of CRISPR/Cas9 on biomedical research and its potential implications in medicine.
在生物医学研究和医学的广泛应用中，人们对操纵基因组有着长期且浓厚的兴趣。实现这一潜力的现有挑战在于无法精确编辑特定的DNA序列。过去为产生靶向双链DNA切割所做的努力，是将诸如锌指和DNA结合蛋白等DNA靶向元件与核酸内切酶融合。然而，这些方法受到设计复杂性以及低效、成本高昂的操作的限制。作为一种潜在的基因组编辑工具，细菌适应性免疫系统的一个分支CRISPR/Cas9的发现带来了轻松进行靶向切割的希望。它的新颖之处在于其RNA引导的核酸内切酶活性，这提高了其效率、可扩展性和易用性。唯一必要的组件是一个Cas9核酸内切酶蛋白和一个针对感兴趣基因定制的RNA分子。自发现以来的短短三年里，这种低应用门槛推动了大量进展。在这篇综述中，我们将讨论CRISPR/Cas9对生物医学研究的影响及其在医学中的潜在意义。
