Advances in Alpha-1 Antitrypsin Gene Therapy.

American Journal of Respiratory Cell and Molecular Biology
Reka Lorincz, David T Curiel

Abstract

AAT (alpha-1 antitrypsin) deficiency (AATD), characterized by low levels of circulating serine protease inhibitor AAT, results in emphysematous destruction of the lung. Inherited serum deficiency disorders, such as hemophilia and AATD, have been considered ideal candidates for gene therapy. Although viral vector-meditated transduction of the liver has demonstrated utility in hemophilia, similar success has not been achieved for AATD. The challenge for AAT gene therapy is achieving protective levels of AAT locally in the lung and mitigating potential liver toxicities linked to systemically administered viral vectors. Current strategies with ongoing clinical trials involve different routes of adeno-associated virus administrations, such as intramuscular and intrapleural injections, to provide consistent therapeutic levels from nonhepatic organ sites. Nevertheless, exploration of alternative methods of nonhepatic sourcing of AAT has been of great interest in the field. In this regard, pulmonary endothelium-targeted adenovirus vector could be a key technical mandate to achieve local augmentation of AAT within the lower respiratory tract, with the potential benefit of circumventing liver toxicities. In addition, incorporation of the...Continue Reading

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Citations

Apr 20, 2021·Frontiers in Cardiovascular Medicine·Jordan R YaronAlexandra R Lucas
Jul 3, 2021·Pharmaceutics·Noha AttiaJose Luis Pedraz

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Methods Mentioned

BETA
transgenic
glycosylation
phage-display
ELISA

Clinical Trials Mentioned

NCT03636347
NCT02168686

Software Mentioned

BioRender

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