基因沉默
核酸
RNA干扰
小干扰RNA
遗传增强
体内
下调和上调
化学
转染
细胞生物学
核糖核酸
生物
生物化学
基因
生物技术
作者
Yangyang Huang,Xujiao Zhou,Y. Zhang,Miao Xie,Fujun Wang,Jing-can Qin,Yongtao Han,Hong Zhang,Chuan Zhang,Jiaxu Hong
标识
DOI:10.1002/advs.202306248
摘要
Abstract Protein degradation techniques, such as proteolysis‐targeting chimeras (PROTACs) and lysosome‐targeting chimeras (LYTACs), have emerged as promising therapeutic strategies for the treatment of diseases. However, the efficacy of current protein degradation methods still needs to be improved to address the complex mechanisms underlying diseases. Herein, a LYTAC Plus hydrogel engineered is proposed by nucleic acid self‐assembly, which integrates a gene silencing motif into a LYTAC construct to enhance its therapeutic potential. As a proof‐of‐concept study, vascular endothelial growth factor receptor (VEGFR)‐binding peptides and mannose‐6 phosphate (M6P) moieties into a self‐assembled nucleic acid hydrogel are introduced, enabling its LYTAC capability. Small interference RNAs (siRNAs) is then employed that target the angiopoietin‐2 (ANG‐2) gene as cross‐linkers for hydrogel formation, giving the final LYTAC Plus hydrogel gene silencing ability. With dual functionalities, the LYTAC Plus hydrogel demonstrated effectiveness in simultaneously reducing the levels of VEGFR‐2 and ANG‐2 both in vitro and in vivo, as well as in improving therapeutic outcomes in treating neovascular age‐related macular degeneration in a mouse model. As a general material platform, the LYTAC Plus hydrogel may possess great potential for the treatment of various diseases and warrant further investigation.
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