Chemically modified siRNA prolonged RNA interference in renal disease.

@article{citeulike:2235186, abstract = {BACKGROUND: We previously demonstrated that transfection of synthetic short interfering RNAs (siRNAs) targeting against TGF-beta1 could be effective and therapeutic in silencing TGF-beta1 expression in glomerulus, thereby ameliorated the progression of matrix expansion in anti-Thy-1 model of glomerulonephritis. However, a major concern in applying RNAi to gene therapy is the prolonged existence of silencing potential in vivo. METHOD: We examined the duration of siRNA stability in kidney and muscle, and checked the tissue distribution of siRNase, eri-1. Thereafter, we tested the effect of chemically modified siRNA called siSTABLE on progressive glomerulosclerosis model. RESULTS: A single introduction of siRNA for EGFP (siEGFP) or its expression vector into kidney resulted in the reduction of masangial EGFP expression only for up to two weeks, while transfection of siEGFP into the pretibial muscle silenced EGFP expression unexpectedly for more than 90 days. These observations could be explained by the different expression of eri-1 between kidney and muscle. In addition, transfection of ERI-1-resistant siSTABLE for TGF-beta1 significantly reduced glomerular matrix deposition in progressive glomerulosclerosis model.Conclusion: Treatment with siRNA resistant to eri-1 may be effective and promising strategy for progressive renal disease.}, address = {Department of Nephrology, Osaka University Graduate School of Medicine (A8), Suita 565-0871, Japan.}, author = {Takabatake, Y. and Isaka, Y. and Mizui, M. and Kawachi, H. and Takahara, S. and Imai, E. }, citeulike-article-id = {2235186}, doi = {10.1016/j.bbrc.2007.08.189}, issn = {0006-291X}, journal = {Biochem Biophys Res Commun}, keywords = {ckd, gene-therapy}, month = {November}, number = {2}, pages = {432--437}, posted-at = {2008-01-15 14:49:02}, priority = {2}, title = {Chemically modified siRNA prolonged RNA interference in renal disease.}, url = {http://dx.doi.org/10.1016/j.bbrc.2007.08.189}, volume = {363}, year = {2007} }

TY - JOUR ID - citeulike:2235186 L3 - citeulike-article-id:2235186 TI - Chemically modified siRNA prolonged RNA interference in renal disease. JF - Biochem Biophys Res Commun VL - 363 IS - 2 SP - 432 EP - 437 AD - Department of Nephrology, Osaka University Graduate School of Medicine (A8), Suita 565-0871, Japan. SN - 0006-291X N2 - BACKGROUND: We previously demonstrated that transfection of synthetic short interfering RNAs (siRNAs) targeting against TGF-beta1 could be effective and therapeutic in silencing TGF-beta1 expression in glomerulus, thereby ameliorated the progression of matrix expansion in anti-Thy-1 model of glomerulonephritis. However, a major concern in applying RNAi to gene therapy is the prolonged existence of silencing potential in vivo. METHOD: We examined the duration of siRNA stability in kidney and muscle, and checked the tissue distribution of siRNase, eri-1. Thereafter, we tested the effect of chemically modified siRNA called siSTABLE on progressive glomerulosclerosis model. RESULTS: A single introduction of siRNA for EGFP (siEGFP) or its expression vector into kidney resulted in the reduction of masangial EGFP expression only for up to two weeks, while transfection of siEGFP into the pretibial muscle silenced EGFP expression unexpectedly for more than 90 days. These observations could be explained by the different expression of eri-1 between kidney and muscle. In addition, transfection of ERI-1-resistant siSTABLE for TGF-beta1 significantly reduced glomerular matrix deposition in progressive glomerulosclerosis model.Conclusion: Treatment with siRNA resistant to eri-1 may be effective and promising strategy for progressive renal disease. KW - ckd KW - gene-therapy AU - Takabatake, Y AU - Isaka, Y AU - Mizui, M AU - Kawachi, H AU - Takahara, S AU - Imai, E PY - 2007/11/16/ UR - http://dx.doi.org/10.1016/j.bbrc.2007.08.189 ER -