C-5-28

A Magnetically Triggered Gene Expression System
Mediated by Heating of Nanoparticles
Masaki Yamaguchi

Akira Ito

3TE12035Y@s.kyushu-u.ac.jp

akira@chem-eng.kyushu-u.ac.jp

Yoshinori Kawabe

Masamichi Kamihira

kawabe@chem-eng.kyushu-u.ac.jp

kamihira@chem-eng.kyushu-u.ac.jp

Department of Chemical Engineering, Faculty of Engineering, Kyushu University, 744
Motooka, Nishi-ku, Fukuoka 819-0395, Japan

Keywords: Inducible gene expression, Transcriptional amplification, Magnetite nanoparticles,
Heat shock protein promoter, Tetracycline-responsive transactivator
Gene therapy promises a wide range of applications in medicine, including cancer treatment.
Similar to chemotherapy, the therapeutic efficacy depends on the dosage (gene expression level)
and timing. Thus, controlled gene expression is essential for gene therapy. Synthetic biology
focuses on designing artificial gene expression systems. Numerous gene circuits have beendeveloped to control gene expression. Among them, the tetracycline (Tet)-inducible system [1] andheat shock protein promoter system [2] have been used as effective inducible gene expression
systems. Using a synthetic biological approach, we have previously constructed a heat-inducible
transgene expression system incorporating a transcriptional positive feedback loop mediated byTet-inducible system that enhances heat-induced gene expression [3].
Remote activation of target cells to trigger specific gene expression in vivo can provide a useful
research tool and potential means to control gene expression in clinical settings [4]. For thispurpose, nanotechnology is becoming increasingly important in medicine. Magnetite nanoparticles
have been used for drug delivery systems and cancer diagnosis as contrast-enhancement agents inmagnetic resonance imaging. Furthermore, magnetite (Fe 3 O 4 ) particles absorb energy and generateheat in response to an alternating magnetic field (AMF) [5]. Thus, heat generation by AMF
exposure can be a potent tool as a switch to induce target gene expression. Here, we combinedsynthetic biology with nanotechnology to convert a local heating signal using magnetite
nanoparticles and AMF exposure into high-level gene expression at a specific site. We investigated
the in vivo feasibility of this approach for cancer gene therapy using a tumor xenograft model.
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expression system incorporating a positive feedback loop of transcriptional amplification for
hyperthermia-induced gene therapy, Journal of Bioscience and Bioengineering, 114:460-465,
2012.
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Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice, Science,
336:604-608, 2012.
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nanothermotherapy, Nanomedicine (Lond), 3:831-844, 2008.