| Research Abstract |
We designed hammerhead ribozyme targetting TGF-β_1 mRNA which cleaved the synthetic substrate RNA. We developed DNA-RNA chimeric ribozyme, which significantly inhibited growth of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR). DNA-RNA chimeric ribozyme inhibited TGF-β_1 mRNA and protein in VSMC from SHR. DNA-RNA chimeric ribozyme significantly suppressed expression of TGF-β_1, fibronectin, collagen type I mRNAs in mesangial cells from SHR-SP. In vivo experiments, FITC-labeled ribozyme was efficiently distributed in aorta and kidney. DNA-RNA chimeric ribozyme considerably inhibited hypertrophy of renal capirally artery and gromerulosclerosis in SHR-SP in vivo. We are appling DNA-RNA chimeric ribozyme on coronary stenosis after angioplasty in pig, by which efficiency, dosage, and period of treatment will be determined to develop the DNA-RNA chimeric ribozyme to TGF-β_1 as a gene therapy for arterial proliferative diseases and gromerulosclerosis.
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