SERPINA1 and alpha 1-antitrypsin deficiency: Thus far, clinical trials for gene therapy for AATD in humans have demonstrated the safety and feasibility of viral gene transfer for AAT delivery, but have been unable to achieve the high systemic levels of AAT protein required to protect the lung.4 Though it is established that significantly lower levels of AAT are necessary within the lung interstitium and ELF than in the peripheral blood to correct protease-antiprotease imbalance and progressive emphysema, AAV-based gene therapy clinical trials have targeted more accessible peripheral tissues.