Efficient AAV Gene Therapy for Hereditary Lung Diseases

Technology #16294

Enables Robust Gene Transfer to Lung Tissue for Treatment of Cystic Fibrosis

These adeno-associated virus (AAV) modifications enhance mucus penetration and airway epithelium transduction, allowing efficient gene delivery for the treatment of a variety of genetic lung diseases, including cystic fibrosis. Cystic fibrosis is an inherited genetic disorder that afflicts approximately 1 in 3,000 individuals of European descent. A mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR) causes a thick buildup of mucus in the lungs, pancreas and other organs. In the lungs, this mucus clogs airways and traps bacteria, resulting in infections, lung damage and respiratory failure. Gene therapy using AAV is a promising tool for treating cystic fibrosis. However, pre-requisition of large vector dose necessary to achieve therapeutic level with conventional AAV serotypes usually leads to initiation of transient inflammation and consequent immune response toward capsid proteins. Available gene therapy strategies to treat cystic fibrosis – by providing a functional CFTR gene to lung tissue – are largely unable to penetrate the thick mucus layer to reach airway epithelium. In addition, those few virus particles that reach airway epithelial cells demonstrate poor transduction efficiency, limiting the effectiveness of gene therapy as a treatment for the disease. Researchers at the University of Florida have developed a variety of AAV modifications to achieve efficient gene transfer in lung tissue, providing a long-term treatment option for cystic fibrosis patients. By enhancing transduction efficiency and mucus penetration, these AAV modifications will enable development of new gene therapy treatments for a multitude of hereditary lung diseases.


AAV modifications that improve delivery of corrective genes to lung tissue for treatment of cystic fibrosis and other genetic lung disorders


  • Enables AAV penetration through thick layers of lung mucus, ensuring that gene therapy treatment reaches target airway epithelial cells in cystic fibrosis patients
  • Increases viral transduction and integration, facilitating increased long-term expression of corrective genes in lung tissue of hereditary lung disease patients
  • Allows AAV capsids to escape degradation in target cells, decreasing likelihood of a treatment-obstructing immune response


These AAV modifications manipulate the natural plasticity of AAV capsid proteins to overcome limitations in treatment of hereditary lung diseases, such as cystic fibrosis. Limitations in transduction efficiency are reduced by promoting escape from proteasomal degradation and the associated immune response, as well as by increasing expression cassette copy number and subsequent integration into the host genome. Restrictions in the ability of AAV to reach target airway epithelial cells are overcome by increasing capsid hydrophobicity, allowing viral particles to achieve effective mucus penetration. Additionally, this panel of modified vectors combines the beneficial properties of both AAV5 and AAV6 serotypes to improve the ability of these AAV vectors to infect and persist in airway cells, allowing efficient long-term treatment of cystic fibrosis and other genetic lung diseases.