Recombinant elastin-based nanoparticles for targeted gene therapy.

Recombinant elastin-based nanoparticles for targeted gene therapy.
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DOI:
10.1038/gt.2017.54
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发表时间:
2017-10
期刊:
影响因子:
5.1
通讯作者:
Koria P
Koria P
中科院分区:
医学3区
文献类型:
--
作者:
Monfort DA;Koria P

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在病毒中,慢病毒载体由于其高效的基因传递方式而成为流行的基因传递载体。然而,与慢病毒载体相关的基因的非特异性递送可能导致不良的副作用。在这里,我们提出了一种非均质纳米颗粒递送系统,用于靶向递送含有治疗基因的慢病毒颗粒。这种非均质纳米颗粒由低密度脂蛋白受体3 (LDLR3)和角质细胞生长因子(KGF)组成,它们分别与弹性蛋白样多肽(ELPs)、LDLR3- elp和KGF- elp融合。我们的研究结果表明,虽然含有LDLR3-ELP的均质纳米颗粒单独阻断了病毒转导,但含有KGF- elp和LDLR3-ELP的非均质纳米颗粒在表达高水平KGF受体的细胞中比表达低水平KGF受体的细胞中增强了病毒转导。总的来说,这种新设计可能有助于靶向过度表达生长因子(如KGF受体)的特定细胞。
Among viruses, lentiviral vectors have been popular vectors for gene delivery due to their efficient mode of gene delivery. However, the non-specific delivery of genes associated with lentiviral vectors may result in undesirable side effects. Here, we propose a heterogeneous nanoparticle delivery system for targeted delivery of lentiviral particles containing a therapeutic gene. The heterogeneous nanoparticles consist of the low density lipoprotein receptor 3 (LDLR3) and the keratinocyte growth factor (KGF), each fused to elastin-like-polypeptides (ELPs), LDLR3-ELP and KGF-ELP, respectively. Our results show that while homogeneous nanoparticles comprising of LDLR3-ELP alone blocked viral transduction, heterogeneous nanoparticles comprising of KGF-ELP and LDLR3-ELP enhanced viral transduction in cells expressing high levels of the KGF receptors compared to cells expressing low levels of KGF receptors. Overall, this novel design may help with the targeting of specific cells that overexpressed growth factor such as KGF receptors.
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