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磁场控制包封细胞中的基因表达。

Magnetic field-controlled gene expression in encapsulated cells.

机构信息

University of Applied Sciences, FH Campus Wien, Department for Applied Life Sciences, Helmut-Qualtinger-Gasse 2, A-1030 Vienna, Austria.

出版信息

J Control Release. 2012 Mar 28;158(3):424-32. doi: 10.1016/j.jconrel.2011.12.006. Epub 2011 Dec 16.

Abstract

Cell and gene therapies have an enormous range of potential applications, but as for most other therapies, dosing is a critical issue, which makes regulated gene expression a prerequisite for advanced strategies. Several inducible expression systems have been established, which mainly rely on small molecules as inducers, such as hormones or antibiotics. The application of these inducers is difficult to control and the effects on gene regulation are slow. Here we describe a novel system for induction of gene expression in encapsulated cells. This involves the modification of cells to express potential therapeutic genes under the control of a heat inducible promoter and the co-encapsulation of these cells with magnetic nanoparticles. These nanoparticles produce heat when subjected to an alternating magnetic field; the elevated temperatures in the capsules then induce gene expression. In the present study we define the parameters of such systems and provide proof-of-principle using reporter gene constructs. The fine-tuned heating of nanoparticles in the magnetic field allows regulation of gene expression from the outside over a broad range and within short time. Such a system has great potential for advancement of cell and gene therapy approaches.

摘要

细胞和基因治疗具有广泛的潜在应用,但与大多数其他疗法一样,剂量是一个关键问题,这使得调控基因表达成为先进策略的前提。已经建立了几种诱导表达系统,主要依赖于小分子作为诱导剂,如激素或抗生素。这些诱导剂的应用难以控制,对基因调控的影响也很慢。在这里,我们描述了一种在封装细胞中诱导基因表达的新系统。这涉及到修饰细胞,使其在热诱导启动子的控制下表达潜在的治疗基因,并与磁性纳米颗粒共包封这些细胞。这些纳米颗粒在交变磁场中会产生热量,胶囊内的温度升高会诱导基因表达。在本研究中,我们定义了这些系统的参数,并使用报告基因构建体提供了原理证明。在磁场中对纳米粒子进行精细加热,可以在广泛的范围内和短时间内从外部调节基因表达。这种系统在细胞和基因治疗方法的发展方面具有巨大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b6/3329627/5366c79c454c/fx1.jpg

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