Targeting neuronal nitric oxide synthase by a cell penetrating peptide Tat-LK15/siRNA bioconjugate

Jie Peng, Yun Rao, Xue Yang, Ji Jia, Youping Wu, Jianhua Lu, Yuanxiang Tao, Weifeng Tu

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

We developed a cell penetrating peptide (CPP) Tat-LK15, as a siRNA carrier to target nNOS. The feasibility, stability, efficiency and selectivity of this peptide-siRNA complex were evaluated in rat neuronal cells. We also compared the new method with conventional siRNA carrier Lipofectamine™. It was found that the CPP Tat-LK15 effectively and specifically delivered nNOS-siRNA into Rat retinal ganglia (RGC-5) cells and silenced the expression of nNOS. The CPP Tat-LK15 can conjugate with siRNA to form stable complex at a ratio of 2:1 (peptide/siRNA, w/w), which maintained stable in serum for as long as 4 h. The CPP Tat-LK15 was low-toxicity to cells, as the apoptosis rate of treat cells was not increased significantly when the used peptide lower than 10 μg/mL. Moreover, the cellular uptake of nNOS siRNA by Rat Neurons-dorsal spinal cord (RNdsc) cells was also significantly more than naked siRNA by RNdsc cells. The CPP Tat-LK15 was an efficient and stable, and non-cytotoxic siRNA delivery to neurons and effectively silenced the nNOS expression. The CPP Tat-LK15 mediated siRNA delivery was a potential tool to treat neuropathic diseases involving NO or nNOS neurotoxic cascades.

Original languageEnglish (US)
Pages (from-to)153-160
Number of pages8
JournalNeuroscience Letters
Volume650
DOIs
StatePublished - May 22 2017

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Cell penetrating peptides
  • Neuronal nitric oxide synthase (nNOS)
  • Neuropathic pain
  • RNA interference
  • Small interfering RNA

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