Synthesis and characterization of chemically condensed oligoethylenimine containing beta-aminopropionamide linkages for siRNA delivery

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• 作者：Peter J. Tarcha ; Jaroslav Pelisek ; Thomas Merdan ; Jan Waters ; Kent Cheung ; Katharina von Gersdorff ; Carsten Culmsee ; Ernst Wagner
• 关键词：siRNA delivery ; Biodegradable nucleic acid carrier ; Condensation of polyethylenimine
• 刊名：Biomaterials
• 出版年：2007
• 出版时间：September 2007
• 年：2007
• 卷：28
• 期：25
• 页码：3731-3740
• 全文大小：314 K

文摘

Polyethylenimines (PEI) are often inefficient in gene knockdown experiments with small interfering RNA (siRNA), presumably due to the strong complexing properties. A more efficient and potentially degradable oligoethylenimine-based carrier was synthesized by the condensation of 800 molecular weight PEI oligomers with hexanedioldiacrylate. Reaction conditions were chosen such that Michael reaction occurs followed by complete N-acylation of all residual ester bonds resulting in beta-aminopropionamide linkage sites and an average molecular weight of 30,000. Based on NMR analysis, these conditions produced 38 % tertiary amides and 62 % secondary amides, with about 2 % residual carboxylate, presumably from hydrolysis. The ionizable equivalent weight of the carrier increased to 51, compared to a value of 43 for standard PEI. Sensible in vitro knockdown of the luciferase gene in stably transfected HUH7 cells, up to 80 % in comparison to non-specific siRNA, demonstrated its suitability for siRNA delivery.