3'-端肽缀合修饰提高寡核苷酸的血清稳定性

doi:10.5246/jcps.2014.04.029

中国药学(英文版) ›› 2014, Vol. 23 ›› Issue (4): 215-219.DOI: 10.5246/jcps.2014.04.029

3'-端肽缀合修饰提高寡核苷酸的血清稳定性

邹朗, 黄野, 王晓锋, 马元, 刘洋, 关注^*, 张礼和, 杨振军^*

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

收稿日期:2013-05-30 修回日期:2013-08-21 出版日期:2014-04-28 发布日期:2013-08-30
通讯作者: *Corresponding author. Tel.: 86-10-82802503; E-mail: guanzhu_gz@bjmu.edu.cn; yangzj@bjmu.edu.cn
作者简介:*Corresponding author. Tel.: 86-10-82802503; E-mail: guanzhu_gz@bjmu.edu.cn; yangzj@bjmu.edu.cn
基金资助:
Ministry of Science and Technology of China (Grant No. 2012CB720604) and National Natural Science Foundation of China (Grant No. 20932001).

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

Lang Zou, Ye Huang, Xiaofeng Wang, Yuan Ma, Yang Liu, Zhu Guan^*, Lihe Zhang, Zhenjun Yang^*

State Key Laboratory of Natural and Biomimetic Drugs; Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2013-05-30 Revised:2013-08-21 Online:2014-04-28 Published:2013-08-30
Contact: *Corresponding author. Tel.: 86-10-82802503; E-mail: guanzhu_gz@bjmu.edu.cn; yangzj@bjmu.edu.cn
About author:*Corresponding author. Tel.: 86-10-82802503; E-mail: guanzhu_gz@bjmu.edu.cn; yangzj@bjmu.edu.cn
Supported by:
Ministry of Science and Technology of China (Grant No. 2012CB720604) and National Natural Science Foundation of China (Grant No. 20932001).

摘要/Abstract

摘要：

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RNase A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: 小干扰RNA, 血清稳定性, 肽缀合, 核酸酶

Abstract:

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 serumenhanced 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.

Key words: siRNA, Serum stability, Peptide conjugation, Nucleases

中图分类号:

R916

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

邹朗, 黄野, 王晓锋, 马元, 刘洋, 关注, 张礼和, 杨振军. 3'-端肽缀合修饰提高寡核苷酸的血清稳定性[J]. 中国药学(英文版), 2014, 23(4): 215-219.

Lang Zou, Ye Huang, Xiaofeng Wang, Yuan Ma, Yang Liu, Zhu Guan, Lihe Zhang, Zhenjun Yang. Serum stability enhancement of siRNA caused by peptide conjugation at 3'-terminus of sense strand[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(4): 215-219.

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3'-端肽缀合修饰提高寡核苷酸的血清稳定性

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

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