| Autor: |
Lin X; siRNA Therapeutics, Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA., Li L, Wang R, Wilcox D, Zhao X, Song J, Huang X, Hansen TM, Dande P, Wada C, Hubbard RD, Kohlbrenner WM, Fesik SW, Shen Y |
| Jazyk: |
angličtina |
| Zdroj: |
RNA (New York, N.Y.) [RNA] 2011 Apr; Vol. 17 (4), pp. 603-12. Date of Electronic Publication: 2011 Feb 14. |
| DOI: |
10.1261/rna.2546011 |
| Abstrakt: |
Delivering small interfering RNA (siRNA) to tumors is the major technical hurdle that prevents the advancement of siRNA-based cancer therapy. One of the difficulties associated with the development of clinically relevant delivery systems is the lack of reliable tools for monitoring siRNA delivery to tumors in vivo. We describe here a novel, positive-readout system where siRNA-mediated target knockdown elicits a rapid and robust increase of reporter activity. Using the positive-readout system, we created (1) β-galactosidase-based tumor models that allow the detection of target knockdown in 1%-2% of tumor cells and can distinguish between tumor areas where effective target knockdown occurs versus tumor areas that are not accessible to delivery, and (2) luciferase-based tumor models that allow the quantitative assessment of a large number of delivery systems. Using these positive-readout models, we screened a number of literature-described siRNA delivery systems and identified lipid nanoparticles as a promising delivery platform for siRNA-based cancer therapy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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