Biological Properties of a 3′,3″-Bis-Peptide-siRNA Conjugate in Vitro and in Vivo

Xinmeng Fan, Yanfen Zhang, Xinjie Liu, Hongyan He, Yuan MA, Jing Sun, Ye Huang, Xiaofeng Wang, Yun Wu*, Lihe Zhang, Zhenjun Yang*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

12 Citations (Scopus)


This study proposes an effective melanoma small interfering RNA (siRNA), named siMB3, which targets the mRNA of mutant BRAF protein. We found that Bis-pep-siMB3, with peptide KALLAL-conjugated siMB3 at the 3′-termini of both strands, inhibited translation of the target genes and expression of the related protein as effectively as siMB3, but for substantially longer, and the conjugates could alleviate off-target effects. Further studies on the mechanisms of action showed that the stability of Bis-pep-siMB3 in fetal bovine serum improved and the half-life period of Bis-pep-siMB3 was increased 21-fold over that of siMB3. Peptide conjugation could improve the combination of siRNA and cationic lipid vectors. Bis-pep-siMB3 is likely to reach the lysosome earlier and stay longer, and appears to increase the release of siRNA from the endosome. At the animal level, application of Bis-pep-siMB3 showed good therapeutic potential, inhibiting the growth of xenograft tumors in athymic mice slightly better than siMB3 and greatly prolonging the circulating time in vivo. Moreover, it distributed widely in mice. These results show the promising potential of Bis-pep-siRNA conjugates as therapeutic siRNAs for cancer treatment.
Original languageEnglish
Pages (from-to)1131-1142
Number of pages12
JournalBioconjugate Chemistry
Issue number4
Publication statusPublished - 20 Apr 2016


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