NEW REPORTER MOLECULES FOR GENE EXPRESSION

Ut Southwestern Medical Center, Dallas TX

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Gene therapy holds great promise for treatment of cancer. However, there are major problems in terms of assessing the delivery to target tissue, assessing the uniformity (versus heterogeneity) of biodistribution, and determining whether the genes are expressed. We propose to design, evaluate, and apply a novel approach to gene activity detection based on proton contrast MRI. The initial tests will evaluate 3,4-cyclohexenoesculetin-beta-galactopyranoside, marketed commercially as S-GalTM for histology to reveal [unreadable]-galactosidase (beta-gal) activity. Following proof of principle, we will synthesize analogs of this traditional "black" biochemical indicator to optimize characteristics for MRI. We have three specific aims: 1) Investigation of S-Gal as an MRI reporter for [unreadable] -gal activity in vivo in tumor cells, 2) Evaluation of S-Gal to detect beta-gal activity in diverse transfected tumors. 3) Development of enhanced reporter agents (analogs of S-Gal), optimized for MRI