Abstract
Cardiac diseases are the leading cause of mortality in the Western World. Despite significant process in the treatment of cardiovascular diseases, curative treatments remain elusive. In recent years, gene therapy for the treatment of cardiac diseases has emerged as a promising and conceptually novel treatment paradigm. Of all the vectors used for cardiac gene delivery, adeno-associated virus (AAV)-based vectors are the most promising. This is due in part to their nonpathogenic nature, the comparatively low immunogenicity, and their ability to transduce efficiently many of the cell types of the cardiovascular system, in particular cardiomyocytes, resulting in long-term, high-level transgene expression.
Here we review the recent development in the field of AAV gene delivery for cardiac diseases. We will discuss the tropism of the naturally occurring AAV serotypes as well as approaches to drive expression exclusively in specific tissues and cell types using transductional, transcriptional, and posttranscriptional approaches. We will examine the recent advances in large-scale AAV vector production and discuss the immune responses against both the vector and the transgene and what challenges this poses for the successful use of AAV vectors in cardiac gene therapy. We will compare the different approaches to deliver AAV vectors to the heart and will assess the potential of promising gene targets for the treatment of cardiac diseases. Finally, we will describe the status of the promising clinical trials that are currently ongoing in the field of cardiac gene therapy.
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Acknowledgments
We would like to thank Drs Irene Turnbull, Erietta Stelekati, and Mr. Erik Kohlbrenner for carefully reading this manuscript. This work is supported by Leducq Foundation through the Caerus network (RJH), by NIH R01 HL093183 (RJH), HL083156 (RJH), and P20HL100396 (RJH).
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Rapti, K., Hajjar, R.J., Weber, T. (2012). Novel Approaches to Deliver Molecular Therapeutics in Cardiac Disease Using Adeno-Associated Virus Vectors. In: Patterson, C., Willis, M. (eds) Translational Cardiology. Molecular and Translational Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-891-7_12
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