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

doi:10.5246/jcps.2014.04.029

Journal of Chinese Pharmaceutical Sciences ›› 2014, Vol. 23 ›› Issue (4): 215-219.DOI: 10.5246/jcps.2014.04.029

• Original articles • Previous Articles Next Articles

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).

Abstract

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

CLC Number:

R916

Supporting:

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

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