磷酰胺
寡核苷酸
可扩展性
活性成分
组合化学
计算机科学
寡核苷酸合成
纳米技术
材料科学
化学
药理学
医学
生物化学
数据库
DNA
作者
Xianglin Shi,Xuan Zhou,Wuming Yan,William F. Kiesman,Yannick Fillon,Hong Jiang,Firoz D. Antia,Li Xiao,Jing Yang,Armin Delavari,Robert S. Gronke
出处
期刊:Research Square - Research Square
日期:2021-08-06
被引量:1
标识
DOI:10.21203/rs.3.rs-594481/v1
摘要
Abstract The recent explosive growth in the number of oligonucleotide clinical development programs and drug approvals underscores their ability to treat diseases via mRNA regulation. Currently, solid-supported synthesis is limited to ≤ 5 kg (~ 1 mole) batch sizes and the feasibility of liquid-phase syntheses to supply materials of sufficient purity and amount for clinical trials has not been proven. Herein we describe the first convergent synthesis of a full-length 18-mer mixed backbone (PO/PS) 2’-MOE gapmer oligonucleotide by the phosphoramidite approach suitable for use in clinical trials. Techniques described to control impurities during its synthesis can be implemented in common active pharmaceutical ingredient (API) manufacturing facilities and should enable a >10-fold increase in production batch scaling.
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