laura-marquezloza@uiowa.edu
Mentor: Paul McCray, Jr., M.D.
Lab Room: 6320 PBDB
Lab Phone: 319-335-6933

Optimizing Lentiviral Gene Therapy for Cystic Fibrosis

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR encodes an anion channel expressed in many organ systems, however, most morbidity and mortality is due to lung disease. Most current treatments focus on symptom management and treatment of secondary disease, but few therapies are available that restore CFTR function.

Our lab previously demonstrated that delivering a normal copy of CFTR to the airways of CF pigs with a lentivirus, partially restored some of the most important CF phenotypes including increasing anion transport in the airway epithelium, and normalizing pH and bacterial killing ability of the airway surface liquid. To improve the efficiency correction with the lentivirus vector we are exploring several options. For instance, the CF anion transport defect can be rescued by transducing fewer cells with vectors that express CFTR at greater than wildtype expression levels. To investigate this finding, we are comparing the expression levels of codon optimized CFTR sequences that, while retaining the same amino acid sequence, might be more efficiently translated. Similarly, we are comparing different promoters to increase CFTR expression in transduced cells.

Another way to achieve higher CFTR expression levels is to transduce more cells. One of the ways that this can be achieved is by using a viral envelope that allows more ubiquitous entry from the apical side of airway epithelia or increases the vector titer. To this end, we are comparing different viral envelopes that provide higher transduction levels while still producing high viral titers. By approaching the challenge of increasing lentiviral delivery and expression from a variety of angles, we hope to arrive at a strategy that will advance gene therapy as a viable one-time treatment for CF patients.



Cooney AL, Singh BK, Marquez Loza LM, Thornell IM, Hippee CE, Powers LS, et al. Widespread airway distribution and short-term phenotypic correction of cystic fibrosis pigs following aerosol delivery of piggyBac/adenovirus. Nucleic Acids Research. 2018;46(18):9591-600.

Marquez Loza LI, Yuen EC, McCray PB, Jr. Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease. Genes (Basel). 2019;10(3).

Marquez Loza LI, Conney AL, Dong Q, Randak C, Rivella S, Sinn P, McCray PB, Jr. Increased CFTR expression and function from an optimized lentiviral vector for cystic fibrosis gene therapy. Molecular Therapy - Methods & Clinical Development 2021

Honors and Awards

• University of Iow Underrepresented Minority Pre-Comprehensive Exam Mentored Resarch Fellowship (Summer 2018)
• University of Iowa Peditrics Research Day – Poster award (April 2018)
• American Physician Scientist Association Midwest Regional Meeting – Poster award (Jan 2018)
• Underrepresented Minority Pre-Comprehensive Exam Fellowship – Summer 2018
• American Society of Gene and Cell Therapy – Underrepresented Minority Travel Award, 2019, 2020