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磁场辅助基因递送:成就与治疗潜力。

Magnetic field-assisted gene delivery: achievements and therapeutic potential.

机构信息

Institute for Biochemical Research-Histology B-Pathology B, Faculty of Medicine, National University of La Plata, Argentina.

出版信息

Curr Gene Ther. 2012 Apr 1;12(2):116-26. doi: 10.2174/156652312800099616.

DOI:10.2174/156652312800099616
PMID:22348552
Abstract

The discovery in the early 2000's that magnetic nanoparticles (MNPs) complexed to nonviral or viral vectors can, in the presence of an external magnetic field, greatly enhance gene transfer into cells has raised much interest. This technique, called magnetofection, was initially developed mainly to improve gene transfer in cell cultures, a simpler and more easily controllable scenario than in vivo models. These studies provided evidence for some unique capabilities of magnetofection. Progressively, the interest in magnetofection expanded to its application in animal models and led to the association of this technique with another technology, magnetic drug targeting (MDT). This combination offers the possibility to develop more efficient and less invasive gene therapy strategies for a number of major pathologies like cancer, neurodegeneration and myocardial infarction. The goal of MDT is to concentrate MNPs functionalized with therapeutic drugs, in target areas of the body by means of properly focused external magnetic fields. The availability of stable, nontoxic MNP-gene vector complexes now offers the opportunity to develop magnetic gene targeting (MGT), a variant of MDT in which the gene coding for a therapeutic molecule, rather than the molecule itself, is delivered to a therapeutic target area in the body. This article will first outline the principle of magnetofection, subsequently describing the properties of the magnetic fields and MNPs used in this technique. Next, it will review the results achieved by magnetofection in cell cultures. Last, the potential of MGT for implementing minimally invasive gene therapy will be discussed.

摘要

21 世纪初的发现表明,与非病毒或病毒载体结合的磁性纳米颗粒(MNPs)在外磁场存在的情况下,可以极大地增强基因向细胞的转移。这项名为磁转染的技术最初主要是为了提高细胞培养物中的基因转移而开发的,因为细胞培养物比体内模型更简单且更易于控制。这些研究为磁转染的一些独特功能提供了证据。随着研究的不断深入,人们对磁转染的兴趣逐渐扩展到动物模型,并将该技术与另一种技术——磁靶向药物传递(MDT)联系起来。这种组合为治疗癌症、神经退行性疾病和心肌梗死等多种主要疾病提供了开发更有效、更少侵入性基因治疗策略的可能性。MDT 的目标是通过适当聚焦的外部磁场,将功能性化的 MNPs 与治疗药物集中在身体的目标区域。目前,稳定、无毒的 MNP-基因载体复合物的出现为磁性基因靶向(MGT)提供了机会,这是 MDT 的一种变体,其中编码治疗分子的基因而不是分子本身被递送到身体的治疗靶区。本文首先概述了磁转染的原理,随后描述了该技术中使用的磁场和 MNPs 的特性。接下来,将回顾磁转染在细胞培养物中取得的成果。最后,将讨论 MGT 用于实施微创基因治疗的潜力。

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