Khan Sikandar Hayat
Department of Pathology, PNS HAFEEZ Hospital, Pathology E-8, Islamabad, Islamabad 44400, Pakistan.
Mol Ther Nucleic Acids. 2019 Jun 7;16:326-334. doi: 10.1016/j.omtn.2019.02.027. Epub 2019 Apr 3.
The traditional healthcare system is at the doorstep for entering into the arena of molecular medicine. The enormous knowledge and ongoing research have now been able to demonstrate methodologies that can alter DNA coding. The techniques used to edit or change the genome evolved from the earlier attempts like nuclease technologies, homing endonucleases, and certain chemical methods. Molecular techniques like meganuclease, transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs) initially emerged as genome-editing technologies. These initial technologies suffer from lower specificity due to their off-targets side effects. Moreover, from biotechnology's perspective, the main obstacle was to develop simple but effective delivery methods for host cell entry. Later, small RNAs, including microRNA (miRNA) and small interfering RNA (siRNA), have been widely adopted in the research laboratories to replace lab animals and cell lines. The latest discovery of CRISPR/Cas9 technology seems more encouraging by providing better efficiency, feasibility, and multi-role clinical application. This later biotechnology seem to take genome-engineering techniques to the next level of molecular engineering. This review generally discusses the various gene-editing technologies in terms of the mechanisms of action, advantages, and side effects.
传统医疗体系即将踏入分子医学领域。如今,大量的知识以及持续不断的研究已能够证明可以改变DNA编码的方法。用于编辑或改变基因组的技术是从早期的尝试,如核酸酶技术、归巢内切酶和某些化学方法演变而来的。像巨核酸酶、转录激活因子样效应物核酸酶(TALENs)和锌指核酸酶(ZFNs)等分子技术最初作为基因组编辑技术出现。这些最初的技术由于脱靶副作用而具有较低的特异性。此外,从生物技术的角度来看,主要障碍是开发简单而有效的进入宿主细胞的递送方法。后来,包括微小RNA(miRNA)和小干扰RNA(siRNA)在内的小RNA已在研究实验室中被广泛采用,以替代实验动物和细胞系。CRISPR/Cas9技术的最新发现似乎更令人鼓舞,因为它具有更高的效率、可行性和多用途临床应用。这种后来的生物技术似乎将基因组工程技术提升到了分子工程的新高度。本综述总体上从作用机制、优点和副作用方面讨论了各种基因编辑技术。