详细记录  
题名:Photochemical internalization enhances silencing of epidermal growth factor receptor through improved endosomal escape of siRNA
作者:Sabrina Oliveira, Marjan M. Fretz, Anders H?gset, Gert Storm and Raymond M. Schiffelers
来源:Biochimica et Biophysica Acta (BBA) - Biomembranes[IF=4.224], In Press, Corrected Proof, Available online 26 January 2007,
URL :http://dx.doi.org/10.1016/j.bbamem.2007.01.013
日期:070415
摘要: Sabrina Oliveiraa, Marjan M. Fretza, Anders H?gsetb, Gert Storma and Raymond M. Schiffelersa, ,

aDepartment Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80.082, 3508 TB Utrecht, The Netherlands
bPCI Biotech AS, N-0377 Oslo, Norway

Received 22 September 2006; revised 9 January 2007; accepted 11 January 2007. Available online 26 January 2007.

Summary

Photochemical internalization (PCI) has been employed as a tool for site-specific intracellular delivery of a variety of molecules. In this study, for the first time, PCI has been employed to facilitate the endosomal escape of small interfering RNA (siRNA) molecules, which are the functional mediators of RNA interference (RNAi). In order to interact with the machinery that will induce post-transcriptional gene silencing, siRNA molecules need to enter the cytoplasm of the cells. This study shows that one of the important rate-limiting steps of siRNA silencing efficiency is the ability of siRNA molecules and/or complexes to escape from the endosomes into the cytosol of the cells. The target of this study, the epidermal growth factor receptor (EGFR), is known as an attractive target for cancer therapy. In this study, a 10-fold increased efficiency in knockdown of the EGFR protein was obtained when anti-EGFR siRNA treatment was combined with PCI as compared to siRNA treatment alone. The fact that this combined treatment resulted in a stronger silencing efficiency indicates that lower doses of siRNA can be used when PCI is employed to augment siRNA delivery. Lowering doses of siRNA would prevent saturation of the RNAi machinery and reduce off-target effects. In addition, local illumination of target tissue would only induce PCI in the desired cells, which can further increase the specificity of the treatment, supporting PCI as an attractive strategy to improve siRNA silencing efficiency. 8ku 7:

================  评  论  部  分=================

重要性:
分类:(参照 Faculty of 1000 的分类体系)


评语:

评论密码:   返回前页  [全部]