Development of novel gene therapy targeting age-related macular degeneration

在这项研究中，我们开发了安全有效的新型眼部基因传递系统来治疗老年性黄斑变性。通过优化配比，成功制备了稳定的纳米粒子(PDNA-PEI络合物：PEI络合物、PDNA-PEI-γ-PGA络合物：PGA络合物、PDNA-PEI-CS络合物：CS络合物)。PGA复合体和CS复合体表现出与PEI复合体相当的高基因表达。PEI复合体表现出严重的玻璃体凝集和细胞毒性，而PGA复合体和CS复合体表现出无凝集和细胞毒性。我们还研制了siRNA-PEI-γ-PGA(siPGA复合体)。SiPGA复合物显示出与商业载体(脂质体)相当的高度沉默效果，且没有细胞毒性。

In this study, we developed the safe and efficient novel ocular gene delivery system to the age-related macular degeneration. We successfully prepared the stable nanoparticles (pDNA-PEI complex: PEI complex, pDNA-PEI-gamma-PGA complex: PGA complex, pDNA-PEI-CS complex: CS complex) by optimization of the mix ratio. The PGA complex and CS complex showed high gene expression comparable to PEI complex. While PEI complex showed severe agglutination of vitreous body and cytotoxicity, PGA complex and CS complex showed no agglutination of vitreous body and no cytotoxicity. We also developed siRNA-PEI-gamma-PGA (siPGA complexes). The siPGA complexes showed high silencing effect comparable to commercial vector (lipofectamine) without cytotoxicity.