Advances in Alpha-1 Antitrypsin Gene Therapy.

Advances in Alpha-1 Antitrypsin Gene Therapy. Am J Respir Cell Mol Biol. 2020 Jul 15;: Authors: Lorincz R, Curiel DT Abstract Alpha-1 antitrypsin deficiency (AATD), characterized by low levels of circulating serine protease inhibitor alpha-1 antitrypsin (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. While viral vector-meditated transduction of the liver have 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 (AAV) administrations, such as intramuscular and intrapleural injections, to provide consistent therapeutic levels from non-hepatic organ sites. Nevertheless, exploration of alternative methods of non-hepatic sourcing of AAT has been a great interest of the field. In this regard, pulmonary endothelium targeted adenoviral vector (Ad) 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 CRISPR/Cas9 nuclease system into gene delivery technologies, h...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research