American journal of translational research · 2022
A novel peptide ligand-coated nano-siRNA-lipoplex technology for kidney targeted gene therapy.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Liu Xia, Zhang Jiandong, Tang Anna, Xu Liang, Huang Yufeng
Аннотация
OBJECTIVES: Small interfering RNA (siRNA) that silences specific disease-related genes holds the promise for the treatment of renal disease. However, delivery to the intended site of action remains a major obstacle. The goal of this study was to develop glomerulus-specific siRNA particles for targeted gene therapy of kidney diseases.
METHODS: We used a novel nanoparticle-based system comprised of siRNA in cationic liposomes (Lip) coated with non-inhibitory plasminogen activator inhibitor 1R (PAI-1R) that selectively targets glomerular cells and tested it with transforming growth factor-beta 1 (TGF-β1)-siRNA in nephritic rat model.
RESULTS: At the optimized ratio of components, three of PAI-1R, Lip and siRNA formed the compact nanostructured particles with close to neutral surface charge (+5.63 ± 1.45 mV) and relatively uniform size (68.9 ± 4.73 nm). When the fluorescence-conjugated siRNA was used, the labeled siRNA nanoparticles appeared specifically in glomeruli. Targeted delivery of siRNA specific to the TGFβ1 gene reduced elevated TGFβ1 mRNA expression and protein production in glomeruli, but had no effect on TGFβ1 mRNA levels in lung, spleen, artery or renal medulla, and in nephritic rats induced by injection of OX-7, for up to 5 days. PAI-1R-Lip-TGF-β1 siRNA administration significantly reduced increases in glomerular matrix accumulation and expression of PAI-1 and fibronectin.
CONCLUSIONS: We conclude that a single dose of PAI-1R-Lip-TGF-β1 siRNA inhibited glomerular TGF-β1 gene expression thereby ameliorating glomerulosclerosis specifically and efficiently in nephritic rats without affecting most of other organs. The target silencing of genes critical for glomerular diseases may represent a promising treatment strategy for kidney disease.
METHODS: We used a novel nanoparticle-based system comprised of siRNA in cationic liposomes (Lip) coated with non-inhibitory plasminogen activator inhibitor 1R (PAI-1R) that selectively targets glomerular cells and tested it with transforming growth factor-beta 1 (TGF-β1)-siRNA in nephritic rat model.
RESULTS: At the optimized ratio of components, three of PAI-1R, Lip and siRNA formed the compact nanostructured particles with close to neutral surface charge (+5.63 ± 1.45 mV) and relatively uniform size (68.9 ± 4.73 nm). When the fluorescence-conjugated siRNA was used, the labeled siRNA nanoparticles appeared specifically in glomeruli. Targeted delivery of siRNA specific to the TGFβ1 gene reduced elevated TGFβ1 mRNA expression and protein production in glomeruli, but had no effect on TGFβ1 mRNA levels in lung, spleen, artery or renal medulla, and in nephritic rats induced by injection of OX-7, for up to 5 days. PAI-1R-Lip-TGF-β1 siRNA administration significantly reduced increases in glomerular matrix accumulation and expression of PAI-1 and fibronectin.
CONCLUSIONS: We conclude that a single dose of PAI-1R-Lip-TGF-β1 siRNA inhibited glomerular TGF-β1 gene expression thereby ameliorating glomerulosclerosis specifically and efficiently in nephritic rats without affecting most of other organs. The target silencing of genes critical for glomerular diseases may represent a promising treatment strategy for kidney disease.