用于超极化氙磁共振成像的基因编码报告器。
Genetically encoded reporters for hyperpolarized xenon magnetic resonance imaging.
机构信息
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.
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.
出版信息
Nat Chem. 2014 Jul;6(7):629-34. doi: 10.1038/nchem.1934. Epub 2014 Apr 28.
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.
磁共振成像（MRI）能够实现对完整生物体的解剖结构和功能的高分辨率非侵入式观察。然而，以前与基因表达相关的关键生物过程的 MRI 报告器受到传统（1）H MRI 固有低分子灵敏度的限制。通过使用诸如惰性气体氙气等超极化核，可以克服这一限制，但以前作用于此类核的报告器是合成的。在这里，我们引入了用于超极化（129）Xe MRI 的第一个基因编码报告器。这些可表达的报告器基于气穴（GVs），这是某些浮质微生物表达的气体结合蛋白纳米结构。我们表明 GVs 能够与氙气进行化学交换饱和转移相互作用，这使得在皮摩尔浓度下能够进行化学放大的 GV 检测（与用于（1）H MRI 的可比结构相比，提高了 100 到 10000 倍）。我们证明了 GVs 可用作异源表达基因表达指示剂和 MRI 实验中外源化学靶向标签，这些实验是在活细胞上进行的。
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