Co-delivery of small interfering RNA and plasmid DNA using a polymeric vector incorporating endosomolytic oligomeric sulfonamide.
Co-delivery of small interfering RNA and plasmid DNA using a polymeric vector incorporating endosomolytic oligomeric sulfonamide.
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DOI：
10.1016/j.biomaterials.2011.03.042
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发表时间：
2011-07
期刊：
影响因子：
14
通讯作者：
Bae, You Han
中科院分区：
文献类型：
--
作者：
Kang, Han Chang;Bae, You Han
阳离子聚合物是小干扰RNA （siRNA）的潜在细胞内载体。与质粒DNA （pDNA）相比，siRNA链的短而刚性往往导致在与载体聚合络合后形成更大、更松散的颗粒，反过来，对靶mrna的沉默效果很差。辅助性聚阴离子pDNA与siRNA结合形成紧凑的纳米级多聚体。当C/A（阳离子/阴离子）比为2和5时，聚l -赖氨酸(PLL)/siRNA- pgfp和PLL/siRNA- pgfp -OSDZ（用于内体溶解的寡聚磺胺嘧啶（OSDZ））配合物产生的颗粒大小为90-150 nm，表面电荷为15-45 mV，而PLL/siRNA配合物在相同的C/A比下产生的颗粒大小为1-2 μm。PLL/siRNA-pGFP （C/ a2）复合物比C/ a2形成的复合物具有更高的特异性基因沉默（50-90% vs. 10-25%）。PLL/siRNA-pGFP-OSDZ （C/ a2）复合物比PLL/siRNA-pGFP （C/ a2）复合物（50%）更显著地改善了特异性基因沉默（90%），证明了OSDZ的潜在作用。与PLL/siRNA-pGFP （C/ a2）复合物相比，PLL/siRNA-pGFP （C/ a2）复合物具有更高的特异性基因沉默。在PLL/siRNA-pGFP-OSA复合物中使用的其他具有不同pKa的寡聚磺胺（OSA）也能引起有效的基因沉默。PLL/siRNA-pGFP复合物中的pGFP在不干扰siRNA的情况下成功表达了GFP蛋白。总之，本研究表明，长pDNA有助于有效形成纳米级siRNA颗粒，OSA增强了特异性基因沉默。在单一核酸载体配方中，siRNA和pDNA的共同递送是可行的，可以最大化治疗效果或包括治疗或诊断功能。
Cationic polymers are potential intracellular carriers for small interfering RNA (siRNA). The short and rigid nature of an siRNA chain often results in larger and more loosely packed particles compared to plasmid DNA (pDNA) after complexing with carrier polycations, and in turn, poor silencing effects are seen against the target mRNAs. A helper polyanion, pDNA, was incorporated along with siRNA to form compact nanosized polyplexes. At C/A (cation/anion) ratios of 2 and 5, poly(L-lysine) (PLL)/siRNA-pGFP and PLL/siRNA-pGFP-OSDZ (oligomeric sulfadiazine (OSDZ) for endosomolysis) complexes produced particles 90–150 nm in size with a 15–45 mV surface charge, while PLL/siRNA complexes yielded particles 1–2 μm in size at the same C/A ratios. The PLL/siRNA-pGFP (C/A 2) complexes showed significantly higher specific gene silencing (50–90% vs. 10–25%) than the complexes formed at C/A 5. PLL/siRNA-pGFP-OSDZ (C/A 2) complexes improved the specific gene silencing (90%) more dramatically than PLL/siRNA-pGFP (C/A 2) complexes (50%), demonstrating a potential role for OSDZ. PLL/siRNA-pGFP-OSDZ (C/A 2) complexes sustained higher specific gene silencing compared with PLL/siRNA-pGFP (C/A 2) complexes. Other oligomeric sulfonamides (OSA) with varying pKa used in PLL/siRNA-pGFP-OSA complexes also caused effective gene silencing. The pGFP in the PLL/siRNA-pGFP complexes successfully expressed GFP protein without interfering with the siRNA. In conclusion, this study demonstrates that long pDNA helps effectively form nanosized siRNA particles and that OSA enhances specific gene silencing. In a single nucleic acid carrier formulation, co-delivery of siRNA and pDNA is feasible to maximize therapeutic effects or to include therapeutic or diagnostic functionalities.
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影响因子：
14
作者：
Kang, Han Chang;Kang, Ho-Jung;Bae, You Han
通讯作者：
Bae, You Han
影响因子：
10.8
作者：
Chono, Sumio;Li, Shyh-Dar;Conwell, Christine C.;Huang, Leaf
通讯作者：
Huang, Leaf
影响因子：
10.8
作者：
Gary, Dana J.;Puri, Nitin;Won, You-Yeon
通讯作者：
Won, You-Yeon
DOI：
10.1016/j.bbrc.2008.04.097
发表时间：
2008-08-01
影响因子：
3.1
作者：
Mukai, Hidefumi;Kawakami, Shigeru;Hashida, Mitsuru
通讯作者：
Hashida, Mitsuru
影响因子：
10.8
作者：
Fahrmeir, Julia;Gunther, Michael;Ogris, Manfred
通讯作者：
Ogris, Manfred