title: Magnetic field-controlled gene expression in encapsulated cells.
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.
authors.affiliation: University of Applied Sciences, FH Campus Wien, Department for Applied Life Sciences, Helmut-Qualtinger-Gasse 2, A-1030 Vienna, Austria.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Ortner
authors.forename: Cornelius
authors.initials: C
authors.lastname: Kaspar
authors.forename: Christian
authors.initials: C
authors.lastname: Halter
authors.forename: Lars
authors.initials: L
authors.lastname: Töllner
authors.forename: Olga
authors.initials: O
authors.lastname: Mykhaylyk
authors.forename: Johann
authors.initials: J
authors.lastname: Walzer
authors.forename: Walter H
authors.initials: WH
authors.lastname: Günzburg
authors.forename: John A
authors.initials: JA
authors.lastname: Dangerfield
authors.forename: Christine
authors.initials: C
authors.lastname: Hohenadl
authors.forename: Thomas
authors.initials: T
authors.lastname: Czerny
mesh_terms: D005290:Ferric Compounds / Q000008:administration & dosage*; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D057809:HEK293 Cells; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D006979:Hyperthermia, Induced; D008156:Luciferases / Q000235:genetics; D060526:Magnetic Fields; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D011108:Polymers / Q000737:chemistry; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D006360:Heat-Shock Proteins; D011108:Polymers; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; C000499:ferric oxide; D008156:Luciferases