A secreted enzyme reporter system for MRI.
A secreted enzyme reporter system for MRI.
复制标题
DOI：
10.1002/anie.200906712
复制
发表时间：
2010-05-25
影响因子：
16.6
通讯作者：
Jasanoff, Alan
中科院分区：
文献类型：
--
作者：
Westmeyer, Gil G.;Durocher, Yves;Jasanoff, Alan
“”
An important goal in modern biology is to understand how molecular processes commonly studied at the cellular level give rise to physiological functions in complex tissues and organisms. Noninvasive imaging of gene expression patterns in whole animals could provide information critical to this end but current methods lack sensitivity and spatiotemporal precision. Enzymatic reporter systems detectable by magnetic resonance imaging (MRI) address these limitations by combining the relatively high spatial and temporal resolution of MRI with the ability of each genetically-expressed enzyme to generate many MRI-detectable product molecules.[1, 2] A challenge with imaging-based detection of some of the most popular reporter enzymes is the need to deliver MRI probes to their sites of action within cells. Here we describe a new reporter gene system for MRI that relieves this problem by harnessing an extracellular enzyme, the mammalian secreted alkaline phosphatase (SEAP).SEAP is a truncated, secreted variant of placental alkaline phosphatase (PLAP), and is widely used as a stable and heterologously expressable reporter enzyme in conjunction with optically absorbant, fluorescent, or luminescent substrates.[3] To detect SEAP activity optimally by MRI, we modified an existing sensor for adenosine (Ado), the product of SEAP’s hydrolysis of phosphorylated adenosine derivatives. In this system, the reporter enzyme is therefore detected through its generation of product molecules, as opposed to its activity on an MRI contrast agent directly. The approach is reversible by removal or degradation of Ado, nondestructive to the Ado sensor, and relatively fast, because SEAP substrates can be used at concentrations well above their Km values without affecting background MRI signal (Fig. 1a).
登录
查看更多内容
影响因子：
3.3
作者：
Chen, JW;Pham, W;Bogdanov, A
通讯作者：
Bogdanov, A
影响因子：
3.2
作者：
Yigit, Mehmet Veysel;Mazumdar, Debapriya;Lu, Yi
通讯作者：
Lu, Yi
影响因子：
15
作者：
Yoo, Byunghee;Pagel, Marty D.
通讯作者：
Pagel, Marty D.
影响因子：
2.5
作者：
Matsumoto, Yuri;Jasanoff, Alan
通讯作者：
Jasanoff, Alan
影响因子：
15
作者：
Aime, Silvio;Fedeli, Franco;Terreno, Enzo
通讯作者：
Terreno, Enzo