PDF(Pubmed)
Abstract：
This review considers research into the treatment of Usher syndrome, a deaf-blindness syndrome inherited in an autosomal recessive manner. Usher syndrome mutations are markedly heterogeneous, involving many different genes, and research grants are limited due to minimal patient populations. Furthermore, gene augmentation therapies are impossible in all but three Usher syndromes as the cDNA sequence exceeds the 4.7 kb AAV packaging limit. It is, therefore, vital to focus research efforts on alternative tools with the broadest applicability. The CRISPR field took off in recent years following the discovery of the DNA editing activity of Cas9 in 2012. New generations of CRISPR tools have succeeded the original CRISPR/Cas9 model to enable more sophisticated genomic amendments such as epigenetic modification and precise sequence alterations. This review will evaluate the most popular CRISPR tools to date: CRISPR/Cas9, base editing, and prime editing. It will consider these tools in terms of applicability (in relation to the ten most prevalent USH2A mutations), safety, efficiency, and in vivo delivery potential with the intention of guiding future research investment.
摘要：
这篇综述考虑了对Usher综合征治疗的研究，一种常染色体隐性遗传的聋盲综合征。Usher综合征的突变具有明显的异质性,涉及许多不同的基因，和研究补助金是有限的，由于最少的患者人群。此外，基因增强疗法在除三种Usher综合征外的所有患者中都是不可能的，因为cDNA序列超过4.7kbAAV包装极限。是的,因此,将研究工作集中在具有最广泛适用性的替代工具上至关重要。在2012年发现Cas9的DNA编辑活性后，CRISPR领域近年来开始腾飞。新一代的CRISPR工具已经取代了原始的CRISPR/Cas9模型，从而实现了更复杂的基因组修正，如表观遗传修饰和精确的序列改变。这篇综述将评估迄今为止最受欢迎的CRISPR工具：CRISPR/Cas9，基础编辑，和主要编辑。它将在适用性方面考虑这些工具（与十个最普遍的USH2A突变相关），安全,效率,和体内递送潜力，旨在指导未来的研究投资。
