First in vivo base-editing trial shows promise.
First in vivo base-editing trial shows promise.
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首次体内碱基编辑试验显示出希望。
DOI：
10.1016/j.ymthe.2023.12.001
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Han,Renzhi
中科院分区：
文献类型：
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作者：
Han,Renzhi
自2013年首次报道人类细胞中的CRISPR-Cas9基因编辑以来，1，2 CRISPR基因组编辑已成为许多人类疾病的令人兴奋的治疗平台。全球首个CRISPR-Cas9基因编辑疗法CASGEVY分别于2023年11月16日和12月8日获得英国监管机构和美国食品药品监督管理局（FDA）的批准，这是一个历史性的里程碑。CASGEVY由Vertex Pharmaceuticals和CRISPR Therapeutics开发，用于治疗镰状细胞病和b-地中海贫血。通过在实验室中电穿孔合成的指导RNA（gRNA）和化脓性链球菌Cas9蛋白，编辑从患者骨髓中分离的造血干细胞（HPSC）中的BCL 11 A，CASGEVY增强了胎儿形式血红蛋白的表达。然后将编辑的HPSC输回给患者。具有里程碑意义的批准CASGEVY预示着一个新的时代的药物。与亲本Cas9基因编辑不同，碱基编辑诱导更精确的碱基转换，而不会产生双链DNA断裂。3，4由Verve Therapeutics开发的领先的心血管疾病（CVD）基础编辑治疗药物（VERV-101）于2022年在新西兰进入血脂控制临床试验。5低密度脂蛋白胆固醇（LDL-C）循环水平升高是CVD的关键风险因素。最近降低胆固醇的治疗进展大大降低了CVD的发病率。然而，目前的药物需要每天口服药丸或频繁注射。永久性基因编辑提供的一次性解决方案可能会改变CVD预防的游戏规则。
Since the first report of CRISPR-Cas9 gene editing in human cells in 2013, 1, 2 CRISPR genome editing has emerged as an exciting therapeutic platform for numerous human diseases. The approval of the world’s first CRISPR-Cas9 gene editing therapy, CASGEVY, by the UK’s regulator on November 16, 2023 and the US Food and Drug Administration (FDA) on December 8, 2023, was a historic milestone. CASGEVY is developed by Vertex Pharmaceuticals and CRISPR Therapeutics for the treatment of sickle cell disease and b-thalassemia. Through editing BCL11A in hematopoietic stem cells (HPSCs) isolated from the patient’s bone marrow via electroporation of a synthetic guide RNA (gRNA) and Streptococcus pyogenes Cas9 protein in the lab, CASGEVY enhances the expression of a fetal form of hemoglobin. The edited HPSCs are then transfused back to patients. The landmark approval of CASGEVY heralds a new era of medicines.Pioneered by Dr. David R. Liu at Harvard University, base editing induces more precise base conversion without creating double-stranded DNA breaks, unlike parental Cas9 gene editing. 3, 4 A leading baseediting therapy drug for cardiovascular disease (CVD) developed by Verve Therapeutics (VERV-101) entered clinical trials for blood lipid control in New Zealand in 2022. 5 Elevated circulating levels of lowdensity lipoprotein cholesterol (LDL-C) are a key risk factor for CVD. Recent therapeutic advances in lowering cholesterol considerably reduced the incidence of CVD. However, current medicines require daily oral pills or frequent injections. A one-time solution offered by permanent gene editing could be a game changer for CVD prevention.