Abstract
Chronic pulmonary hypertension (PH) is associated with right ventricular failure and high mortality regardless of the underlying disease. Currently, therapies can improve clinical outcomes in specific subsets of patients, but have little impact on the progression of pulmonary vascular remodeling. Upon new advances in vector development and delivery techniques, gene therapy is a novel strategy in this field with the potential of overcoming the main limitations of approved drug therapies: modulation of novel anti-remodeling targets and selective pulmonary vasculature targeting with minimal systemic effects. In the recent years, several reports have shown that gene transfer to the pulmonary vascular system is feasible in rodent models of PH. Our group has focused on the translation of airway delivery of viral vectors in small and large animals. Here, we describe a procedure to achieve vector transduction at the distal vasculature in animal models of PH and the methods to evaluate the outcomes of this intervention as a promising new approach in pulmonary vascular diseases.
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Acknowledgments
This work is supported by NIH P50 HL112324, R01 HL119046, R01 HL117505, R01 HL128099, R01 HL129814, R01HL131404, & T32 HL007824 (R. J. H.), and a Transatlantic Leducq Foundation grant. We would like to acknowledge the Gene Therapy Resource Program (GTRP) of the National Heart, Lung, and Blood Institute, National Institutes of Health for providing some of the gene vectors used in these studies. J.A. was supported by the Fundacion Alfonso Martin-Escudero. N.H. was supported by the French Federation of Cardiology.
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Aguero, J., Hadri, L., Hammoudi, N., Leonardson, L., Hajjar, R.J., Ishikawa, K. (2017). Inhaled Gene Transfer for Pulmonary Circulation. In: Ishikawa, K. (eds) Cardiac Gene Therapy. Methods in Molecular Biology, vol 1521. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6588-5_24
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DOI: https://doi.org/10.1007/978-1-4939-6588-5_24
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