Abstract

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.

Document Type

Article

Publication Date

3-15-2018

Notes/Citation Information

Published in Scientific Reports, v. 8, article no. 4638, p. 1-10.

© The Author(s) 2018

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Digital Object Identifier (DOI)

https://doi.org/10.1038/s41598-018-22993-4

Funding Information

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.

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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.

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Supplementary Information

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