Intracellular signal-responsive gene carrier for cell-specific gene expression.
Intracellular signal-responsive gene carrier for cell-specific gene expression.
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DOI：
10.1021/bm0493887
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发表时间：
2005-03
影响因子：
6.2
通讯作者：
K. Kawamura;Jun Oishi;Jeong-Hun Kang;K. Kodama;T. Sonoda;M. Murata;T. Niidome;Y. Katayama
中科院分区：
文献类型：
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作者：
K. Kawamura;Jun Oishi;Jeong-Hun Kang;K. Kodama;T. Sonoda;M. Murata;T. Niidome;Y. Katayama
我们设计了肽-聚合物缀合物（CPCCtat）作为新型基因载体，可以响应细胞内 caspase-3 信号控制基因表达。该载体由不带电荷的主聚合物链和阳离子肽侧链组成，其中包括caspase-3的底物序列和HIV-1 Tat的蛋白转导结构域序列。在本研究中，CPCCtat通过静电相互作用与DNA形成紧密复合物，在这种状态下基因表达被完全抑制。相反，由于阳离子部分从 CPCCtat 上裂解，复合物在 caspase-3 存在下分解。该事件导致基因表达的激活。我们的结果还表明，由于 CPCCtat 的细胞可渗透肽侧链，该复合物可以被递送到活细胞中。这种具有 CPCCtat 的细胞内信号响应系统将可用于细胞特异性基因表达系统。
We designed a peptide-polymer conjugate (CPCCtat) as a novel gene carrier that could control gene expression responding to the intracellular caspase-3 signal. This carrier consists of an uncharged main polymer chain and a cationic peptide side chain, which includes the substrate sequence of caspase-3 and the protein transduction domain sequence of HIV-1 Tat. In the present study, CPCCtat formed a tight complex with DNA through an electrostatic interaction, and in this state the gene expression was totally suppressed. In contrast, the complex disintegrated in the presence of caspase-3 due to cleavage of the cationic portion from CPCCtat. This event led to an activation of gene expression. Our results also indicate that the complex can be delivered into living cells due to the cell-permeable peptide side chain of CPCCtat. This intracellular signal-responsive system with CPCCtat will be useful for the cell-specific gene expression system.