Research into gene therapy for heart failure has gained renewed interest as a result of improved safety and availability of adeno-associated viral vectors (AAV). While magnetic resonance imaging (MRI) is standard for functional assessment of gene therapy outcomes, quantitation of gene transfer/expression relies upon tissue biopsy, fluorescence or nuclear imaging. Imaging of gene expression through the use of genetically encoded chemical exchange saturation transfer (CEST)-MRI reporter genes could be combined with clinical cardiac MRI methods to comprehensively probe therapeutic gene expression and subsequent outcomes. The CEST-MRI reporter gene Lysine Rich Protein (LRP) was cloned into an AAV9 vector and either administered systemically via tail vein injection or directly injected into the left ventricular free wall of mice. Longitudinal in vivo CEST-MRI performed at days 15 and 45 after direct injection or at 1, 60 and 90 days after systemic injection revealed robust CEST contrast in myocardium that was later confirmed to express LRP by immunostaining. Ventricular structure and function were not impacted by expression of LRP in either study arm. The ability to quantify and link therapeutic gene expression to functional outcomes can provide rich data for further development of gene therapy for heart failure.
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MHV is supported by NIH 1R01HL28592-01 and NIH P20GM103527-07sub5039, AAG is supported by Maryland Stem Cell Research Foundation (MSCRFII-0042). JFA is supported by NIH 1R01NS091329-01.
All data is maintained on a server at UC Berkeley and will be made available to interested researchers upon request. Interested parties should contact corresponding author.
Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-22993-4.
Meier, Shelby; Gilad, Assaf A.; Brandon, Jason Anthony; Qian, Chenghao; Gao, Erhe; Abisambra, Jose F.; and Vandsburger, Moriel, "Non-Invasive Detection of Adeno-Associated Viral Gene Transfer Using a Genetically Encoded CEST-MRI Reporter Gene in the Murine Heart" (2018). Physiology Faculty Publications. 127.