A versatile reducible polycation-based system for efficient delivery of a broad range of nucleic acids.
A versatile reducible polycation-based system for efficient delivery of a broad range of nucleic acids.
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DOI：
10.1093/nar/gni085
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发表时间：
2005-05-24
影响因子：
14.9
通讯作者：
Seymour LW
中科院分区：
文献类型：
--
作者：
Read ML;Singh S;Ahmed Z;Stevenson M;Briggs SS;Oupicky D;Barrett LB;Spice R;Kendall M;Berry M;Preece JA;Logan A;Seymour LW
评价了基于由组氨酸和聚赖氨酸残基组成的可还原聚阳离子（HIS RPC）的合成载体递送核酸的能力。初步实验表明，具有至少70%组氨酸含量的基于RPC的载体介导有效水平的基因转移，而不需要内体溶解剂氯喹。在一系列细胞类型中观察到显著的基因转移，与金标准合成载体25 kDa PEI相比，转染细胞的百分比增加高达5倍。与25 kDa PEI相比，HIS RPC还介导其他核酸的有效转移，包括PC-3细胞中编码绿色荧光蛋白的mRNA和大鼠背根神经节细胞神经元有丝分裂后培养物中针对神经营养因子受体p75 NTR的siRNA。实验，以提高细胞内谷胱甘肽和多光子荧光显微镜捕获的细胞图像的线性分析强调，参数，如分子量和速率的切割HIS RPC的转染活性的重要因素。总之，这些结果表明，HIS RPC代表了一种新的和通用类型的载体，其可用于有效的细胞质递送广泛的核酸。这应该能够使用单一类型的基于聚阳离子的载体来评估不同的治疗策略或治疗策略的组合。
Synthetic vectors based on reducible polycations consisting of histidine and polylysine residues (HIS RPCs) were evaluated for their ability to deliver nucleic acids. Initial experiments showed that RPC-based vectors with at least 70% histidine content mediated efficient levels of gene transfer without requirement for the endosomolytic agent chloroquine. Significant gene transfer was observed in a range of cell types achieving up to a 5-fold increase in the percentage of transfected cells compared to 25 kDa PEI, a gold standard synthetic vector. In contrast to 25 kDa PEI, HIS RPCs also mediated efficient transfer of other nucleic acids, including mRNA encoding green fluorescent protein in PC-3 cells and siRNA directed against the neurotrophin receptor p75NTR in post-mitotic cultures of rat dorsal root ganglion cell neurons. Experiments to elevate intracellular glutathione and linear profiling of cell images captured by multiphoton fluorescent microscopy highlighted that parameters such as the molecular weight and rate of cleavage of HIS RPCs were important factors in determining transfection activity. Altogether, these results demonstrate that HIS RPCs represent a novel and versatile type of vector that can be used for efficient cytoplasmic delivery of a broad range of nucleic acids. This should enable different or a combination of therapeutic strategies to be evaluated using a single type of polycation-based vector.
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影响因子：
5.1
作者：
Dash, PR;Read, ML;Seymour, LW
通讯作者：
Seymour, LW
DOI：
10.1016/s0006-291x(03)00029-9
发表时间：
2003-02-14
影响因子：
3.1
作者：
Higuchi, H;Yamashita, T;Tohyama, M
通讯作者：
Tohyama, M
影响因子：
3.5
作者：
Boeckle, S;von Gersdorff, K;Ogris, M
通讯作者：
Ogris, M
DOI：
10.1073/pnas.87.11.4033
发表时间：
1990-06-01
影响因子：
11.1
作者：
COTTEN, M;LANGLEROUAULT, F;BIRNSTIEL, ML
通讯作者：
BIRNSTIEL, ML
影响因子：
5.3
作者：
Davidson, TJ;Harel, S;Troy, CM
通讯作者：
Troy, CM