Abstract
The development of noninvasive technologies for remote control of gene expression has received increased attention for their therapeutic potential in clinical scenarios, including cancer, neurological disorders, immunology, tissue engineering, as well as developmental biology research. Near-infrared (NIR) light is a suitable source of energy that can be employed to pattern transgene expression in plasmonic cell constructs. Gold nanoparticles tailored to exhibit a plasmon surface band absorption peaking at NIR wavelengths within the so called tissue optical window (TOW) can be used as fillers in fibrin-based hydrogels. These biocompatible composites can be loaded with cells harboring heat-inducible gene switches. NIR laser irradiation of the resulting plasmonic cell constructs causes the local conversion of NIR photon energy into heat, achieving spatially restricted patterns of transgene expression that faithfully match the illuminated areas of the hydrogels. In combination with cells genetically engineered to harbor gene switches activated by heat and dependent on a small-molecule regulator (SMR), NIR-responsive hydrogels allow reliable and safe control of the spatiotemporal availability of therapeutic biomolecules in target tissues.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsSpringer Nature is developing a new tool to find and evaluate Protocols. Learn more
References
Parsell DA, Lindquist S (1993) The function of heat-shock proteins in stress tolerance: degradation and reactivation of damaged proteins. Annu Rev Genet 27:437–496
Welch WJ (1993) How cells respond to stress. Sci Am 268:56–64
Cotto JJ, Morimoto RI (1999) Stress-induced activation of the heat-shock response: cell and molecular biology of heat-shock factors. Biochem Soc Symp 64:105–118
Voellmy R (2004) Transcriptional regulation of the metazoan stress protein response. Prog Nucleic Acid Res Mol Biol 78:143–185
Christians ES, Benjamin IJ (2006) Heat shock response: lessons from mouse knockouts. Handb Exp Pharmacol: (172) 139–152
Voellmy R, Ahmed A, Schiller P, Bromley P et al (1985) Isolation and functional analysis of a human 70,000-dalton heat shock protein gene segment. Proc Natl Acad Sci U S A 82:4949–4953
Schiller P, Amin J, Ananthan J, Brown ME et al (1988) Cis-acting elements involved in the regulated expression of a human HSP70 gene. J Mol Biol 203:97–105
Dreano M, Brochot J, Myers A, Cheng-Meyer C et al (1986) High-level, heat-regulated synthesis of proteins in eukaryotic cells. Gene 49:1–8
Vilaboa N, Voellmy R (2006) Regulatable gene expression systems for gene therapy. Curr Gene Ther 6:421–438
Huang Q, Hu JK, Lohr F, Zhang L et al (2000) Heat-induced gene expression as a novel targeted cancer gene therapy strategy. Cancer Res 60:3435–3439
Vekris A, Maurange C, Moonen C, Mazurier F et al (2000) Control of transgene expression using local hyperthermia in combination with a heat-sensitive promoter. J Gene Med 2:89–96
Locke M, Noble EG, Tanguay RM, Feild MR et al (1995) Activation of heat-shock transcription factor in rat heart after heat shock and exercise. Am J Physiol 268:C1387–C1394
Shastry S, Toft DO, Joyner MJ (2002) HSP70 and HSP90 expression in leucocytes after exercise in moderately trained humans. Acta Physiol Scand 175:139–146
Vilaboa N, Fenna M, Munson J, Roberts SM et al (2005) Novel gene switches for targeted and timed expression of proteins of interest. Mol Ther 12:290–298
Martin-Saavedra FM, Wilson CG, Voellmy R, Vilaboa N et al (2013) Spatiotemporal control of vascular endothelial growth factor expression using a heat-shock-activated, rapamycin-dependent gene switch. Hum Gene Ther Methods 24:160–170
Konig K (2000) Multiphoton microscopy in life sciences. J Microsc 200:83–104
Weissleder R (2001) A clearer vision for in vivo imaging. Nat Biotechnol 19:316–317
Miyako E, Deguchi T, Nakajima Y, Yudasaka M et al (2012) Photothermic regulation of gene expression triggered by laser-induced carbon nanohorns. Proc Natl Acad Sci U S A 109:7523–7528
Cebrian V, Martin-Saavedra F, Gomez L, Arruebo M et al (2013) Enhancing of plasmonic photothermal therapy through heat-inducible transgene activity. Nanomedicine 9:646–656
Martin-Saavedra FM, Cebrian V, Gomez L, Lopez D et al (2014) Temporal and spatial patterning of transgene expression by near-infrared irradiation. Biomaterials 35:8134–8143
Acknowledgment
This work was supported by grants PI12/01698 from Fondo de Investigaciones Sanitarias (FIS, Spanish Ministry of Economy and Competitiveness, MINECO, Spain) and SAF2013-50364-EXP (MINECO, Spain) to N.V.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media New York
About this protocol
Cite this protocol
Martín-Saavedra, F., Vilaboa, N. (2016). Remote Patterning of Transgene Expression Using Near Infrared-Responsive Plasmonic Hydrogels. In: Kianianmomeni, A. (eds) Optogenetics. Methods in Molecular Biology, vol 1408. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3512-3_19
Download citation
DOI: https://doi.org/10.1007/978-1-4939-3512-3_19
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3510-9
Online ISBN: 978-1-4939-3512-3
eBook Packages: Springer Protocols