title: Inhaled Gene Transfer for Pulmonary Circulation.
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.
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, #1030, New York, NY, 10029, USA. jaimeaguero30@hotmail.com.|Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. jaimeaguero30@hotmail.com.
authors.forename: Jaume
authors.initials: J
authors.lastname: Aguero
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, #1030, New York, NY, 10029, USA.
authors.forename: Lahouaria
authors.initials: L
authors.lastname: Hadri
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, #1030, New York, NY, 10029, USA.
authors.forename: Nadjib
authors.initials: N
authors.lastname: Hammoudi
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, #1030, New York, NY, 10029, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Leonardson
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, #1030, New York, NY, 10029, USA.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, #1030, New York, NY, 10029, USA.
authors.forename: Kiyotake
authors.initials: K
authors.lastname: Ishikawa
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D004562:Electrocardiography; D018014:Gene Transfer Techniques; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology; D006439:Hemodynamics; D011652:Pulmonary Circulation / Q000502:physiology*; D013552:Swine; D014161:Transduction, Genetic
keywords: Adeno-associated virus; Airway delivery; Gene therapy; Large animal model; Pulmonary hypertension; Pulmonary vascular disease; Right ventricular failure; Vascular remodeling