ZFIN ID: ZDB-PUB-150904-14
PEG-PLA Nanoparticles facilitate siRNA knockdown in adult zebrafish heart
Diao, J., Wang, H., Chang, N., Zhou, X.H., Zhu, X., Wang, J., Xiong, J.W.
Date: 2015
Source: Developmental Biology   406(2): 196-202 (Journal)
Registered Authors: Xiong, Jing-Wei
Keywords: Heart regeneration, PEG-PLA nanoparticles, Sirna, Zebrafish
MeSH Terms:
  • Animals
  • Cell Proliferation/genetics
  • Cell Proliferation/physiology
  • Dual Specificity Phosphatase 6/genetics
  • Gene Knockdown Techniques/methods*
  • Isoenzymes/genetics
  • Myocardium/cytology
  • Myocardium/metabolism*
  • Nanoparticles/metabolism*
  • Polyethylene Glycols/metabolism*
  • RNA Interference*
  • RNA, Small Interfering/genetics
  • RNA, Small Interfering/metabolism*
  • Retinal Dehydrogenase/genetics
  • Zebrafish/genetics*
PubMed: 26327645 Full text @ Dev. Biol.
The remarkable regenerative capacity of the zebrafish has made it an important model organism for studying heart regeneration. However, current loss-of-function studies are limited by a lack of conditional-knockout and effective gene-knockdown methods for the adult heart. Here, we report a novel siRNA knockdown method facilitated by poly (ethylene glycol)-b-poly (D, l-lactide) (PEG-PLA) nanoparticles. The siRNA-encapsulated nanoparticles successfully entered cells and resulted in remarkable gene-specific knockdown in the adult heart. This effect was demonstrated by down-regulation of the Aldh1a2 and Dusp6 proteins after intrapleural delivery of nanoparticle-encapsulated siRNAs. Furthermore, siRNA-mediated knockdown of Aldh1a2 was sufficient to inhibit myocardial proliferation and decrease the numbers of Gata4-positive cardiomyocytes after ventricular resection. Therefore, the results of this work demonstrate that nanoparticle-facilitated siRNA delivery provides an alternative tool for loss-of-function studies of genes in the adult heart in particular and other organs in general in the adult zebrafish.