title: Genetically encoded reporters for hyperpolarized xenon magnetic resonance imaging.
abstract: Magnetic resonance imaging (MRI) enables high-resolution non-invasive observation of the anatomy and function of intact organisms. However, previous MRI reporters of key biological processes tied to gene expression have been limited by the inherently low molecular sensitivity of conventional (1)H MRI. This limitation could be overcome through the use of hyperpolarized nuclei, such as in the noble gas xenon, but previous reporters acting on such nuclei have been synthetic. Here, we introduce the first genetically encoded reporters for hyperpolarized (129)Xe MRI. These expressible reporters are based on gas vesicles (GVs), gas-binding protein nanostructures expressed by certain buoyant microorganisms. We show that GVs are capable of chemical exchange saturation transfer interactions with xenon, which enables chemically amplified GV detection at picomolar concentrations (a 100- to 10,000-fold improvement over comparable constructs for (1)H MRI). We demonstrate the use of GVs as heterologously expressed indicators of gene expression and chemically targeted exogenous labels in MRI experiments performed on living cells.
authors.affiliation: 1] Miller Research Institute, University of California, Berkeley, Berkeley, California 94720, USA [2] Department of Bioengineering, University of California, Berkeley, Berkeley, California 94720, USA [3] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [4] Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Mikhail G
authors.initials: MG
authors.lastname: Shapiro
authors.affiliation: 1] Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California 94720, USA [2] Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: R Matthew
authors.initials: RM
authors.lastname: Ramirez
authors.affiliation: Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: Sperling
authors.affiliation: Department of Bioengineering, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: George
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: Jinny
authors.initials: J
authors.lastname: Sun
authors.affiliation: 1] Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California 94720, USA [2] Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pines
authors.affiliation: 1] Department of Bioengineering, University of California, Berkeley, Berkeley, California 94720, USA [2] Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Schaffer
authors.affiliation: 1] Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California 94720, USA [2] Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Vikram S
authors.initials: VS
authors.lastname: Bajaj
mesh_terms: D015870:Gene Expression; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D014978:Xenon / Q000737:chemistry*
chemical_list: D014978:Xenon