Maria Hudock
Bioreactor-based Optimization of Inhaled Gene Therapy for Cystic Fibrosis
Abstract
Despite 36 clinical trials, gene therapy for cystic fibrosis (CF), a lethal lung disease, remains elusive. We have developed a bioreactor model of CF airways, comprising bioartificial mucus-coated porcine airway tissue, for screening inhaled nanocarriers of gene therapy. However, it is unknown how nanoparticle uptake compares in porcine and human tissue. Further, principles of nanoparticle design for airway delivery have not been defined. I propose to quantitatively compare the mechanisms of endocytosis (cell uptake) of nanoparticles between porcine and human airway tissue, to determine whether nanoparticle uptake screening in porcine tissue can be used to predict results in human tissue. I will also identify physical properties of nanoparticles that lead to best mucus penetration and tissue uptake, towards design principles for airway delivery. The predictive model and design principles generated here will help translate therapies for CF and other diseases accessible through the lung.
Receiving this fellowship has increased my confidence as an investigator by affirming that I can generate interesting, relevant project ideas, by helping me to practice study planning, and by bolstering me to follow through and work with even more conviction. For this, I am extremely grateful.
