Alpha-1 Antitrypsin Deficiency
Recently, new effective therapy explorations for the treatment of Alpha 1-antitrypsin deficiency (A1AD) have turned to gene therapy. Added by our advanced gene-therapy platform, Creative Biolabs is just the chosen one who has absolute advantages in offering the best gene therapy services for the treatment of A1AD using engineered adeno-associated viruses (AAVs).
Introduction of Alpha-1 Antitrypsin Deficiency
Alpha-1 antitrypsin (A1AT) is a kind of bioactive glycoprotein mainly synthesized in the liver and encoded by the human SERPINA1 gene. As a member of the serpin, it is also referred to as antiproteinase, proteinase inhibitor, and serum trypsin inhibitor due to the inhibitory activity against various proteases. As the most important protease inhibitor in human plasma, AIAT functions as an enzyme inhibitor to protect tissues from enzymatic damage by enzymes of inflammatory cells. A1AD occurs when the level of A1AT is insufficient in the blood or A1AT functional deficiency. A1AD is a relatively common genetic disorder resulting from SERPINA1 gene mutations and generally involves lung disease or liver disease. Severe complications caused by A1AD include lung infections, chronic obstructive pulmonary disease (COPD), cirrhosis, neonatal hepatitis, and hepatocellular carcinoma.
A1AD lacks specific therapies currently, usual approaches aiming at the resultant disease treatments. Augmentation or replacement therapy is preferred, by which blood-derived human A1AT protein is administered intravenously to raise circulating AITA to normal levels and arrest the course of the disease. Some other symptomatic therapies include treatments of A1AD-related lung diseases with bronchodilators, inhaled steroids, and antibiotics for infections, and treatments of A1AD-related liver diseases with liver transplantation.
A1AD Treated by AAV Vector-Based Gene Therapy
Considering A1AD is a monogenetic disorder caused by mutations in the SERPINA1 gene, numerous efforts have been devoted to developing innovative effective gene therapies by the correction of the mutated gene or supplement of the absent gene. Characteristics of tissue tropism, long-expression ability, and low immunogenicity make AAVs vectors ideal vehicles to deliver the normal human SERPINA1 complementary DNA (cDNA) into the pneumonocytes, hepatocytes, and skeletal muscle cells.
Different AAV serotypes and administration strategies have been explored for the gene therapy of A1AD, and many AAV vector-based gene therapy products have proceeded in clinical trials. Compared with conventional therapies, these various promising AAV vector-based gene therapies for A1AD along with proper administration strategies exhibit many advantages, such as single administration, reduced risks and costs, ongoing therapeutic effect, etc.
Figure 1. Concept of intrapleural administration of an adeno-associated virus (AAV) vector coding for alpha-1 antitrypsin. (Chiuchiolo, 2016)
The lung/liver-directed gene therapy using AAV vector holds great promise for treating A1AD. With the efforts of experienced technicians, Creative Biolabs provides customized AAV vector design and other related services for the treatment of A1AD. If you are interested, please contact us, we can customize our offering to meet your specific project needs.
Reference
- Chiuchiolo, M.J.; Crystal, R.G. (2016). Gene Therapy for Alpha-1 Antitrypsin Deficiency Lung Disease. Annals of the American Thoracic Society. 13(Suppl 4): S352-S369.
