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A genetically encoded ß-lactamase reporter for ultrasensitive 129Xe NMR and MRI in mammalian cells

Description:

Hyperpolarized xenon chemical exchange saturation transfer (CEST) contrast agent for molecular imaging

 

Inventor

Ivan Dmochowski, Professor of Chemistry

 

Problem

While genetically encoded optical reporters have enabled biomolecular imaging, the strong scattering of light by tissue is problematic.  Optical reporters are limited to examining single cells and transparent model organisms.  Alternate non-invasive imaging methods, such as magnetic resonance imaging (MRI), are needed for monitoring gene expression and cell migration in vivo.  Furthermore, despite excellent spatiotemporal resolution, 1H MRI reporter genes are limited by low detection sensitivity.

 

Solution

Researchers in the Dmochowski have developed a genetically encoded, single protein reporter for hyperpolarized 129Xe NMR and MRI with high saturation contrast for use in molecular imaging applications.  Hyperpolarized xenon provides enhanced detection sensitivity.  Because 129Xe is nontoxic, it can be safely delivered via inhalation or injection in vivo.  Furthermore, its small size and hydrophobicity allow for interactions with proteins, occupying hydrophobic cores, substrate-binding sites, and channel pores, enabling the study of biological phenomena.  129Xe chemical exchange saturation transfer (CEST) occurs between the aqueous solvent and β-lactamase, either in solution or inside a cell.  Xenon CEST interactions with β-lactamase yield a distinct saturation peak and chemical shift.  The x-ray crystal structure of the binding of xenon to β-lactamase has been elucidated, which will inform the design of additional CEST agents.

  

 

Advantages

•       Nontoxic, readily deliverable to cells and in vivo

•       High molecular sensitivity

•       Noninvasive imaging method

•       High contrast

 

Applications

•       Molecular imaging

•       Contrast agents

•       Elucidate biological processes, normal and diseased physiological states

•       Study cryptic pockets in proteins

 

 

Stage of Development

•       Proof-of-concept

•       In vitro and in vivo testing

 

Intellectual Property

Provisional pending

 

 

Reference Media

Wang Y. et al. Angew. Chemie, 2016.

Roose B.W. et al.  ACS National Meeting, March 2016.  Single-protein reporter for hyperpolarized xenon magnetic resonance imaging.

Dmochowski, I.J. et al.  ACS National Meeting, March 2016.  Xenon: new applications in materials chemistry and biosensing.

 

Desired partnerships

• License

Co-development

 

 

Download PDF

 

Docket #  16-7836 


Patent Information:
For Information, Contact:
Joshua Jeanson
Associate Director, SEAS/SAS Licensing Group
University of Pennsylvania
jeanson@upenn.edu
Inventors:
Ivan Dmochowski
Keywords: