PEG-PLA nanoparticles facilitate siRNA knockdown in adult zebrafish heart.
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.
Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
Jupeng
J
Diao
School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
Hongxia
H
Wang
Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
Nannan
N
Chang
Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
Xiao-Hai
XH
Zhou
Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China.
Xiaojun
X
Zhu
School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
Jun
J
Wang
Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China. Electronic address: jingwei_xiong@pku.edu.cn.
Jing-Wei
JW
Xiong
D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D054642:Dual Specificity Phosphatase 6 / Q000235:genetics; D055785:Gene Knockdown Techniques / Q000379:methods*; D007527:Isoenzymes / Q000235:genetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D053758:Nanoparticles / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000235:genetics; D015027:Zebrafish / Q000235:genetics*
D007527:Isoenzymes; D034741:RNA, Small Interfering; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D000080924:Aldehyde Dehydrogenase 1 Family; D050697:Retinal Dehydrogenase; D054642:Dual Specificity Phosphatase 6
Heart regeneration; PEG–PLA nanoparticles; Zebrafish; siRNA