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siRNA targeting UBE2v1 is a gene therapy approach delivered via lipid nanoparticles (LNPs) designed to counteract fibrosis progression in diabetic kidney disease (DKD). It functions by selectively modulating the lysine-63 ubiquitination pathway through the downregulation of the UBE2v1 gene, which plays a key role in driving tubulointerstitial fibrosis. The LNPs, composed of ionizable cationic lipids, cholesterol, helper lipids, and PEG-lipids, have demonstrated effective entry into HK2 renal tubular cells and no cytotoxicity in vitro. In vivo studies in diabetic DBA2J mice showed that intraperitoneal injection of siRNA-LNPs significantly reduced renal UBE2v1 expression without causing significant inflammatory infiltration or tissue alterations.
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