【回乡偶记】ZFN又遭重创？

我为什么要说“又”呢？——二当家

朴实的中国人民即使在春节假期为全世界的和平操碎了心

万事皆有因，当然这位大哥之前已经很惨了

简单回顾MPS(黏多糖贮积症) I/II：分别由IDUA/IDS基因突变引起编码的IDUA或IDS酶活的缺失，造成有毒的代谢废物糖胺聚糖(GAGs)在溶酶体聚积最终引起组织和器官损伤，这是一类X连锁遗传的代谢性疾病

那么这种单基因疾病能不能像血友病那样进行酶替代治疗（ERT）呢？

Sangamo Therapeutics slumps on double normal volume on the heelsof preliminary data from two clinical trials evaluating two of its zinc fingernuclease (ZFN) candidates in patients with mucopolysaccharidosis (MPS),an inherited group of disorders in which the body cannot break down large sugarmolecules. The results were presented at the WORLDSymposium inOrlando, FL.

Interim data fromthe Phase 1/2 CHAMPIONS studyassessing SB-913 in patients with MPS type II only showed only a small increasein the key enzyme, called IDS, which plays the principal role in breaking downthe sugar molecules.

Integration的效率是一个原因

Cohort 3中的6号是唯一的IDS活性+urinay CAGs升高的，虽然integration的结果还未知，代价就是轻微的ALT升高，泼尼松可以解决；后续发生脐疝的SAE，但这个就和药物无关了

这个小结写的就是春秋笔法了

Interim data fromthe Phase 1/2 EMPOWERS studyevaluating SB-318 in MPS type 1 patients also failed to show much of an effecton a key enzyme called IDUA or urinary glycosaminoglycans (GAGs), the sugarsthat build up in tissues due to the absence of or disfunction in IDUA.Increased levels of GAGs in the urine indicate that the sugars are being brokendown and excreted.

ZFN is a gene editing technology that uses a DNA-cutting enzymeattached to zinc finger DNA-binding proteins to recognize and edit specificsequences of DNA. Its major rival is CRISPR/Cas9 which is considered to be easier to use, cheaper and more precise.

下载链接：

EMPOWERS: Phase 1/2 clinical trial of SB-318 ZFN in vivo genome editing for MPS I

February 7, 2019

https://investor.sangamo.com/static-files/3ac6cfd1-9c60-4464-b609-8f6cfa9a3a0e

MPS II (SB-913) and MPS I (SB-318) Phase 1/2 Interim Data Conference Call

February 7, 2019

https://investor.sangamo.com/static-files/0e1dafa7-c558-4b4e-a057-616a721f5b1d

CHAMPIONS: Phase 1/2 clinical trial of SB-913 ZFN in vivo genome editing for MPS II

February 7, 2019

https://investor.sangamo.com/static-files/33fe548e-1139-40dd-a5ec-612af46b3751