Chechik Lyuba, Martin Ophelie, Soutoglou Evi
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France.
Front Cell Dev Biol. 2020 May 8;8:319. doi: 10.3389/fcell.2020.00319. eCollection 2020.
Genome editing by Clustered Regularly Inter Spaced Palindromic Repeat (CRISPR) associated (Cas) systems has revolutionized medical research and holds enormous promise for correcting genetic diseases. Understanding how these Cas nucleases work and induce mutations, as well as identifying factors that affect their efficiency and fidelity is key to developing this technology for therapeutic uses. Here, we discuss recent studies that reveal how DNA sequence and chromatin structure influences the different steps of genome editing. These studies also demonstrate that a deep understanding of the balance between error prone and error free DNA repair pathways is crucial for making genome editing a safe clinical tool, which does not induce further mutations to the genome.
由成簇规律间隔短回文重复序列（CRISPR）相关（Cas）系统进行的基因组编辑彻底改变了医学研究，并为纠正遗传疾病带来了巨大希望。了解这些Cas核酸酶如何发挥作用并诱导突变，以及识别影响其效率和保真度的因素，是将该技术用于治疗用途的关键。在此，我们讨论了最近的研究，这些研究揭示了DNA序列和染色质结构如何影响基因组编辑的不同步骤。这些研究还表明，深入了解易错和无错DNA修复途径之间的平衡对于使基因组编辑成为一种安全的临床工具至关重要，该工具不会对基因组诱导进一步的突变。
