Magnetic field-controlled gene expression in encapsulated cells

J Control Release. 2012 Mar 28;158(3):424-32. doi: 10.1016/j.jconrel.2011.12.006. Epub 2011 Dec 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ferric Compounds / administration & dosage*
  • Gene Expression Regulation*
  • Genes, Reporter / genetics
  • Green Fluorescent Proteins / genetics
  • HEK293 Cells
  • Heat-Shock Proteins / genetics
  • Humans
  • Hyperthermia, Induced
  • Luciferases / genetics
  • Magnetic Fields*
  • Metal Nanoparticles / administration & dosage*
  • Polymers / chemistry
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / metabolism

Substances

  • Ferric Compounds
  • Heat-Shock Proteins
  • Polymers
  • RNA, Messenger
  • Green Fluorescent Proteins
  • ferric oxide
  • Luciferases