Aerosol-Mediated Delivery of Recombinant Adenovirus to the Airways of Nonhuman Primates
- 1 December 1995
- journal article
- research article
- Published by Mary Ann Liebert Inc in Human Gene Therapy
- Vol. 6 (12) , 1587-1593
- https://doi.org/10.1089/hum.1995.6.12-1587
Abstract
At present, it is conceivable that gene therapy of the cystic fibrosis airway epithelium is possible using the direct transfer of a functional human cystic fibrosis transmembrane conductance regulator (CFTR) gene to a wide variety of patients' tracheo-bronchial cells. Here we describe a novel approach (aerosolization) to deliver a replication-deficient adenovirus carrying the CFTR gene (Ad.CFTR) to the airways. Results obtained in vitro and in Rhesus monkeys suggest that the delivery of recombinant adenovirus as an aerosol is feasible and is not associated with severe toxicity after single or double administration depending on the Ad.CFTR dose. This study supports the concept of aerosolization as a delivery method for adenovirus-mediated lung gene therapy. With the goal of delivering therapeutic genes to lung epithelia in a noninvasive, safe and practicable fashion, we have evaluated whether aerosolization of recombinant adenovirus could be a means of administration to the airways of Rhesus monkeys. A replication-defective (E1¯, E3¯) adenovirus carrying an expression cassette for the human cystic fibrosis transmembrane conductance regulator (CFTR) gene was chosen as the test system. Our results indicate that this route of administration may represent a way to treat lung diseases by recombinant adenovirus.Keywords
This publication has 15 references indexed in Scilit:
- Trans-Complementation of E1-Deleted Adenovirus: A New Vector to Reduce the Possibility of Codissemination of Wild-Type and Recombinant AdenovirusesHuman Gene Therapy, 1995
- Acute Responses of Non-Human Primates to Airway Delivery of an Adenovirus Vector Containing the Human Cystic Fibrosis Transmembrane Conductance Regulator cDNAHuman Gene Therapy, 1994
- In VivoEvaluation of the Safety of Adenovirus-Mediated Transfer of the Human Cystic Fibrosis Transmembrane Conductance Regulator cDNA to the LungHuman Gene Therapy, 1994
- Safety and efficacy of repetitive adenovirus–mediated transfer of CFTR cDNA to airway epithelia of primates and cotton ratsNature Genetics, 1994
- Lung Gene Therapy: In Vivo Adenovirus-Mediated Gene Transfer to Rhesus Monkey Airway EpitheliumHuman Gene Therapy, 1994
- Diversity of airway epithelial cell targets for in vivo recombinant adenovirus-mediated gene transfer.Journal of Clinical Investigation, 1993
- Cystic fibrosis: molecular biology and therapeutic implicationsScience, 1992
- In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epitheliumCell, 1992
- Identification of the Cystic Fibrosis Gene: Chromosome Walking and JumpingScience, 1989
- Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNAScience, 1989