Preclinical assessment of improved lentiviral vectors for gene and cell therapy of pulmonary alveolar proteinosis

Congenital pulmonary alveolar proteinosis (PAP) caused by mutations in GM-CSF receptor α chain (CSF2RA) represents a rare, life-threatening disease characterized by the accumulation of phospholipids and proteins in the lungs due to a functional insufficiency of alveolar macrophages. So far, therapy options are limited, but recent data suggest that a gene therapy approach based on the intratracheal application of gene-corrected macrophages may be feasible. To this aim, we have generated SIN-lentiviral constructs expressing the codon-optimized human CSF2RA-cDNA in combination with EGFP (Lv.EFS.CSF2RA.EGFP) or the…