title: Genetic manipulation of iron biomineralization enhances MR relaxivity in a ferritin-M6A chimeric complex.
abstract: Ferritin has gained significant attention as a potential reporter gene for in vivo imaging by magnetic resonance imaging (MRI). However, due to the ferritin ferrihydrite core, the relaxivity and sensitivity for detection of native ferritin is relatively low. We report here on a novel chimeric magneto-ferritin reporter gene - ferritin-M6A - in which the magnetite binding peptide from the magnetotactic bacteria magnetosome-associated Mms6 protein was fused to the C-terminal of murine h-ferritin. Biophysical experiments showed that purified ferritin-M6A assembled into a stable protein cage with the M6A protruding into the cage core, enabling magnetite biomineralisation. Ferritin-M6A-expressing C6-glioma cells showed enhanced (per iron) r2 relaxivity. MRI in vivo studies of ferritin-M6A-expressing tumour xenografts showed enhanced R2 relaxation rate in the central hypoxic region of the tumours. Such enhanced relaxivity would increase the sensitivity of ferritin as a reporter gene for non-invasive in vivo MRI-monitoring of cell delivery and differentiation in cellular or gene-based therapies.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100 Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Radoul
authors.affiliation: Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel.
authors.forename: Limor
authors.initials: L
authors.lastname: Lewin
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100 Israel.
authors.forename: Batya
authors.initials: B
authors.lastname: Cohen
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100 Israel.
authors.forename: Roni
authors.initials: R
authors.lastname: Oren
authors.affiliation: Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Popov
authors.affiliation: Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel.
authors.forename: Geula
authors.initials: G
authors.lastname: Davidov
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100 Israel.
authors.forename: Moriel H
authors.initials: MH
authors.lastname: Vandsburger
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100 Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Harmelin
authors.affiliation: Department of Chemical Engineering and Ilse Katz Institute for Nanoscale Science and Technology Ben-Gurion University of the Negev, 84105 Beer-Sheva, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Bitton
authors.affiliation: Institut des Molécules et Matériaux du Mans (IMMM), UMR CNRS 6283 Université du Maine, Avenue Olivier Messiaen, 72085 Le Mans Cedex France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Greneche
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100 Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Neeman
authors.affiliation: Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel.
authors.forename: Raz
authors.initials: R
authors.lastname: Zarivach
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000378:metabolism*; D052203:Ferrosoferric Oxide / Q000378:metabolism*; D017930:Genes, Reporter; D005818:Genetic Engineering; D008279:Magnetic Resonance Imaging; D051379:Mice; D008958:Models, Molecular; D009368:Neoplasm Transplantation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D005290:Ferric Compounds; D011993:Recombinant Fusion Proteins; C000499:ferric oxide; D001052:Apoferritins; D052203:Ferrosoferric Oxide