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无毒,可生物降解的超分支多 (β-氨基) 对于高效的siRNA传递和基因沉默

Ying Jie Ooi¹, Chongquan Huang^1,2, Kieran Lau¹

¹School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637459, Singapore.

ACS applied materials & interfaces

|March 7, 2024

概括

研究人员开发了新型的超分支聚β氨基 (pBAE),用于高效的RNA干扰 (RNAi) 基因沉默. 这些新的非病毒载体显示了毒性降低和小干扰RNA (siRNA) 在挑战细胞中的增强传递.

科学领域:

生物材料科学生物材料科学
基因治疗基因治疗
纳米技术纳米技术

背景情况:

RNA干扰 (RNAi) 提供了治疗潜力,但面临着交付挑战.
非病毒载体,如聚β氨基 (pBAE) 是有前途的,但往往需要高剂量,引发毒性问题.
优化pBAE结构对于有效和安全的siRNA传递至关重要.

研究的目的:

为高效的siRNA凝聚和基因沉默设计和优化超分支的pBAE.
与商业转染剂相比,评估这些新型pBAE的性能.
评估这些pBAE在向难以转移的原始细胞传递siRNA方面的潜力.

主要方法:

一系列具有不同单体组合和分支密度的超分支pBAE的合成和表征.
在体外评估siRNA凝聚,细胞毒性,细胞吸收和HeLa细胞和初级神经细胞中的基因沉默效率.
领先的pBAE候选物 (h(A2B3) -1) 与Lipofectamine 2000 的比较.
将生物可降解二硫化物键纳入聚合物骨干,以提高细胞相容性.

主要成果:

一种超分支的pBAE,h(A2B3)-1,在显著较低的聚合物/siRNA比率和siRNA剂量下显示出优异的siRNA凝聚和基因沉默.
h(A2B3)-1在HeLa细胞中表现出较低的细胞毒性和比Lipofectamine 2000更高的传染效率.
在难以转移的原发皮质神经元 (34.8%的淘汰) 和寡干细胞原生细胞 (53.4%的淘汰) 中实现了有效的基因沉默.
加入二硫化物键进一步提高了细胞相容性,而不会影响转化效率.

结论:

超分支的pBAE,特别是h(A2B3)-1,是siRNA传递的高度有效的非病毒载体.
这些新型聚合物为安全有效的RNAi介导基因沉默提供了有前途的解决方案,具有临床翻译的潜力.
这项研究为开发下一代非病毒基因传递系统提供了宝贵的见解.

关键词:

可生物降解,可生物降解.基因沉默是对基因进行沉默的方法.聚乙氨基) 是一种聚乙氨基.主要的神经细胞是主要的神经细胞.siRNA的传递方式

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