Article

Chemically modified siRNA prolonged RNA interference in renal disease.

Department of Nephrology, Osaka University Graduate School of Medicine (A8), Suita 565-0871, Japan.
Biochemical and Biophysical Research Communications (impact factor: 2.48). 12/2007; 363(2):432-7. DOI:10.1016/j.bbrc.2007.08.189 pp.432-7
Source: PubMed

ABSTRACT 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.
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.
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.

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Keywords

applying RNAi
 
different expression
 
ERI-1-resistant siSTABLE
 
expression vector
 
glomerular matrix deposition
 
major concern
 
masangial EGFP expression
 
matrix expansion
 
pretibial muscle silenced EGFP expression
 
progressive glomerulosclerosis model
 
progressive glomerulosclerosis model.Conclusion
 
progressive renal disease
 
prolonged existence
 
promising strategy
 
single introduction
 
siRNA resistant
 
siRNAs
 
siRNase
 
synthetic short
 
TGF-beta1 expression