Lentiviral Vector Based Gene Therapy for Respiratory Diseases

Inefficient pulmonary gene transfer is a major factor that has limited the development of a clinically suitable gene therapy for cystic fibrosis (CF). While Sendai virus‐mediated gene transfer to airway epithelial cells is highly efficient, the short duration of expression and strong immunogenicity have rendered Sendai virus‐based vectors ineffective for CF gene therapy.
We have developed a lentiviral vector pseudotyped with the Sendai virus F and HN envelope proteins (rSIV.F/HN), to deliver a normal copy of the CFTR cDNA into the genomic DNA of airway epithelial cells of patients with CF.
With this vector, we have demonstrated efficient and lifelong transduction in the airways of multiple species. In addition it shows the ability to redose, efficiently transduces all of the major airway epithelial cell types and demonstrates restoration of CFTR function in intestinal organoids.
A mutation‐agnostic gene therapy for CF may benefit patients who are genetically ineligible for CFTR modulator therapy, as well as eligible patients who experience adverse reactions or suboptimal responses to this therapy.
The above data support the progression of BI 3720931 towards the clinic, with a first‐in‐human trial in final preparation for regulatory submission.