Magnetic field-controlled gene expression in encapsulated cells

JOURNAL OF CONTROLLED RELEASE

卷:158

Article

Ortner, Viktoria^1,2  Kaspar, Cornelius³  Halter, Christian⁴  Toellner, Lars³  Mykhaylyk, Olga⁵  Walzer, Johann⁴  Guenzburg, Walter H.^3,6  Dangerfield, John A.^3,6,7  Hohenadl, Christine³  Czerny, Thomas^1,2 

[1] Univ Appl Sci, Dept Appl Life Sci, A-1030 Vienna, Austria

[2] Univ Vet Med, Dept Biomed Sci, A-1210 Vienna, Austria

[3] Univ Vet Med, Inst Virol, Dept Pathobiol, A-1210 Vienna, Austria

[4] Univ Appl Sci, Dept Engn, A-1100 Vienna, Austria

[5] Tech Univ Munich, Inst Expt Oncol, Dept Pathobiol, Klinikum Rechts Isar, D-81675 Munich, Germany

[6] Univ Vet Med, Inst Virol, Christian Doppler Lab Gene Therapeut Vector Dev, A-1210 Vienna, Austria

[7] SG Austria, Singapore 138668, Singapore

关键词: Magnetic nanoparticles;    Hyperthermia;    Inducible gene expression;    Cell encapsulation;    Cell therapy;    Gene therapy;   

DOI  :  10.1016/j.jconrel.2011.12.006

来源: Elsevier

【 摘 要 】

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. (C) 2011 Elsevier B. V. All rights reserved.

【 授权许可】

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