PUBLICATION
Tumor-targeted in vivo gene silencing via systemic delivery of cRGD-conjugated siRNA
- Authors
- Liu, X., Wang, W., Samarsky, D., Liu, L., Xu, Q., Zhang, W., Zhu, G., Wu, P., Zuo, X., Deng, H., Zhang, J., Wu, Z., Chen, X., Zhao, L., Qiu, Z., Zhang, Z., Zeng, Q., Yang, W., Zhang, B., Ji, A.
- ID
- ZDB-PUB-140917-6
- Date
- 2014
- Source
- Nucleic acids research 42(18): 11805-17 (Journal)
- Registered Authors
- Chen, Xiaohui, Zhao, Lingfeng
- Keywords
- none
- MeSH Terms
-
- Humans
- Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors
- Vascular Endothelial Growth Factor Receptor-2/genetics
- Zebrafish/embryology
- Female
- Mice, Inbred BALB C
- RNA, Small Interfering/administration & dosage*
- RNA, Small Interfering/chemistry
- HeLa Cells
- Peptides, Cyclic/administration & dosage*
- Peptides, Cyclic/analysis
- Peptides, Cyclic/chemistry
- Neovascularization, Physiologic
- Animals
- Cells, Cultured
- RNA Interference*
- Gene Knockdown Techniques
- Neoplasms/blood supply
- Neoplasms/therapy*
- Cell Line, Tumor
- Human Umbilical Vein Endothelial Cells/metabolism
- Mice, Nude
- PubMed
- 25223783 Full text @ Nucleic Acids Res.
Citation
Liu, X., Wang, W., Samarsky, D., Liu, L., Xu, Q., Zhang, W., Zhu, G., Wu, P., Zuo, X., Deng, H., Zhang, J., Wu, Z., Chen, X., Zhao, L., Qiu, Z., Zhang, Z., Zeng, Q., Yang, W., Zhang, B., Ji, A. (2014) Tumor-targeted in vivo gene silencing via systemic delivery of cRGD-conjugated siRNA. Nucleic acids research. 42(18):11805-17.
Abstract
RNAi technology is taking strong position among the key therapeutic modalities, with dozens of siRNA-based programs entering and successfully progressing through clinical stages of drug development. To further explore potentials of RNAi technology as therapeutics, we engineered and tested VEGFR2 siRNA molecules specifically targeted to tumors through covalently conjugated cyclo(Arg-Gly-Asp-d-Phe-Lys[PEG-MAL]) (cRGD) peptide, known to bind αvβ3 integrin receptors. cRGD-siRNAs were demonstrated to specifically enter and silence targeted genes in cultured αvβ3 positive human cells (HUVEC). Microinjection of zebrafish blastocysts with VEGFR2 cRGD-siRNA resulted in specific inhibition of blood vessel growth. In tumor-bearing mice, intravenously injected cRGD-siRNA molecules generated no innate immune response and bio-distributed to tumor tissues. Continuous systemic delivery of two different VEGFR2 cRGD-siRNAs resulted in down-regulation of corresponding mRNA (55 and 45%) and protein (65 and 45%) in tumors, as well as in overall reduction of tumor volume (90 and 70%). These findings demonstrate strong potential of cRGD-siRNA molecules as anti-tumor therapy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping