申请人:Alnylam Pharmaceuticals, Inc.
公开号:US20150073133A1
公开(公告)日:2015-03-12
The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent.
本发明涉及iRNA药剂,其中最好包括一个单体,其中核糖基团已被其他核糖以外的基团所取代,该基团还包括一个具有一个或多个连接基团的连接件,其中至少一个连接基团是可断裂的连接基团。连接件可以连接到所选的基团,例如配体,例如靶向或递送基团,或改变物理性质的基团。可断裂的连接基团是足够稳定的连接基团,以在细胞外允许将治疗上有益量的iRNA药剂(例如单链或双链iRNA药剂),通过可断裂的连接基团与靶向剂耦合,以靶向细胞,但在进入靶细胞后被断裂以释放iRNA药剂从靶向剂中。