唤醒沉睡的基因：激活胎儿珠蛋白治疗β-地中海贫血症。

Wake-up Sleepy Gene: Reactivating Fetal Globin for β-Hemoglobinopathies.

机构信息

School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW) Sydney, Sydney, New South Wales, Australia; Innovative Genomics Institute, University of California, Berkeley, CA, USA; Present address: Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.

School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW) Sydney, Sydney, New South Wales, Australia.

出版信息

Trends Genet. 2018 Dec;34(12):927-940. doi: 10.1016/j.tig.2018.09.004. Epub 2018 Oct 1.

DOI:10.1016/j.tig.2018.09.004

PMID:30287096

Abstract

Disorders in hemoglobin (hemoglobinopathies) were the first monogenic diseases to be characterized and remain among the most common and best understood genetic conditions. Moreover, the study of the β-globin locus provides a textbook example of developmental gene regulation. The fetal γ-globin genes (HBG1/HBG2) are ordinarily silenced around birth, whereupon their expression is replaced by the adult β-globin genes (HBB primarily and HBD). Over 50 years ago it was recognized that mutations that cause lifelong persistence of fetal γ-globin expression ameliorate the debilitating effects of mutations in β-globin. Since then, research has focused on therapeutically reactivating the fetal γ-globin genes. Here, we summarize recent discoveries, focusing on the influence of genome editing technologies, including CRISPR-Cas9, and emerging gene therapy approaches.

摘要

血红蛋白（血红蛋白病）紊乱是第一个被描述的单基因疾病，仍然是最常见和最被理解的遗传条件之一。此外，对β-珠蛋白基因座的研究提供了发育基因调控的典型范例。胎儿γ-珠蛋白基因（HBG1/HBG2）通常在出生时沉默，随后被成人β-珠蛋白基因（主要是 HBB 和 HBD）取代。50 多年前，人们就认识到导致胎儿γ-珠蛋白表达持续存在的突变可以减轻β-珠蛋白突变的致残影响。从那时起，研究就集中在治疗性地重新激活胎儿γ-珠蛋白基因上。在这里，我们总结了最近的发现，重点介绍了包括 CRISPR-Cas9 在内的基因组编辑技术和新兴的基因治疗方法的影响。