Serum stability enhancement of siRNA caused by peptide conjugation at 3'-terminus of sense strand  

3'-端肽缀合修饰提高寡核苷酸的血清稳定性(英文)

作　　者：邹朗 黄野[1] 王晓锋[1] 马元[1] 刘洋 关注[1] 张礼和[1] 杨振军[1] 

机构地区：[1]北京大学医学部天然药物及仿生药物国家重点实验室药学院药物化学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2014年第4期215-219,共5页中国药学（英文版）

基　　金：Ministry of Science and Technology of China(Grant No.2012CB720604);National Natural Science Foundation of China(Grant No.20932001)

摘　　要：RNA interference has been widely used for gene therapy of various infectious diseases and malignant tumors. However, its poor stability in serum has limited further clinic application. Here, we found that stability of siRNA in serum enhanced obviously when 3′-terminus of sense strand （siRNA-pS） was conjugated with peptide, while same conjugation at 3′-terminus of antisense strand brought no such effects. And it was also found that only the peptide residue in siRNA-pS could be cut off by RNase A. All these results indicated that nucleases in serum prefer to invade siRNA duplex through the 3′-end of sense strand.RNA干扰被广泛用于传染性疾病及恶性肿瘤的基因治疗领域,但体内稳定性较差限制了其在临床上的应用。本文报道了在siRNA正义链的3'-端缀合不同长度的肽片段均能够明显提高血清稳定性,而在siRNA反义链的3'-端缀合相同的肽片段则对血清稳定性没有影响。血清中的RNaseA能够选择性水解siRNA正义链3'-末端缀合的肽片段,从而得到原siRNA片段,但反义链3'-末端缀合肽缀合物则不能在血清中得到原siRNA片段。该结果进一步证明RNase A对siRNA双链的进攻具有方向性。

关 键 词：SIRNA Serum stability Peptide conjugation NUCLEASES 

分 类 号：R450[医药卫生—治疗学]