作者
Alfica Sehgal, Scott Barros, Lacramioara Ivanciu, Brian Cooley, June Qin, Tim Racie, Julia Hettinger, Mary Carioto, Yongfeng Jiang, Josh Brodsky, Harsha Prabhala, Xuemei Zhang, Husain Attarwala, Renta Hutabarat, Don Foster, Stuart Milstein, Klaus Charisse, Satya Kuchimanchi, Martin A Maier, Lubo Nechev, Pachamuthu Kandasamy, Alexander V Kel'in, Jayaprakash K Nair, Kallanthottathil G Rajeev, Muthiah Manoharan, Rachel Meyers, Benny Sorensen, Amy R Simon, Yesim Dargaud, Claude Negrier, Rodney M Camire, Akin Akinc
发表日期
2015/5
期刊
Nature medicine
卷号
21
期号
5
页码范围
492-497
出版商
Nature Publishing Group US
简介
Hemophilia A and B are inherited bleeding disorders characterized by deficiencies in procoagulant factor VIII (FVIII) or factor IX (FIX), respectively. There remains a substantial unmet medical need in hemophilia, especially in patients with inhibitory antibodies against replacement factor therapy, for novel and improved therapeutic agents that can be used prophylactically to provide effective hemostasis. Guided by reports suggesting that co-inheritance of prothrombotic mutations may ameliorate the clinical phenotype in hemophilia,,,,,,,,, we developed an RNA interference (RNAi) therapeutic (ALN-AT3) targeting antithrombin (AT) as a means to promote hemostasis in hemophilia. When administered subcutaneously, ALN-AT3 showed potent, dose-dependent, and durable reduction of AT levels in wild-type mice, mice with hemophilia A, and nonhuman primates (NHPs). In NHPs, a 50% reduction in AT levels was …
学术搜索中的文章
A Sehgal, S Barros, L Ivanciu, B Cooley, J Qin, T Racie… - Nature medicine, 2015