AAV8hAAT(AVL)

AAV8hAAT(AVL) is a gene therapy investigational product designed for the treatment of **alpha-1 antitrypsin (AAT) deficiency**. It utilizes an **adeno-associated virus serotype 8 (AAV8) vector** to deliver a gene encoding a specially engineered, oxidation-resistant form of human alpha-1 antitrypsin (AAT(AVL), with M351V and M358L substitutions for enhanced resistance to inactivation by oxidants). The therapy is intended to result in **persistent, high-level expression** of functional AAT protein, primarily in the liver, which is then secreted into the circulation to protect the lungs from neutrophil protease-mediated damage, thereby potentially preventing early-onset emphysema in AAT-deficient individuals. Preclinical studies in mice demonstrated long-term expression, functional anti-protease activity even in the presence of oxidative stress, and a favorable safety profile with no significant vector-related toxicity or morbidity. The approach aims to offer a one-time, durable increase in AAT levels and address shortcomings of current protein replacement therapy[1][6][4][7][9].