2006 Fiscal Year Final Research Report Summary
Gene therapy for progressive kidney diseases using siRNA
| Project/Area Number |
17590827
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
ISAKA Yoshitaka Osaka University, Graduate School of Medicine, Endowed chair Associate Professor, 医学系研究科, 寄附講座助教授 (00379166)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IMAI Enyu Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (00223305)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | siRNA / glomerulonephritis / eri-1 / TGF-beta |
|---|
| Research Abstract |
Background ; We previous demonstrated that transfection of synthetic short interfering RNAs (siRNAs) targeting against TGF-β1 could be effective and therapeutic in silencing TGF-β1 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 siSTABLE^<TM> 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^<TM> for TGF-β significantly reducedglomerular matrix deposition in progressive glomerulosclerosis model. Conclusion ; Treatment with siRNA resistant to eri-1 may be effective and promising strategy for progressive renal disease.
|
Research Products
(5 results)
