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Address: 6320 PBDB
Phone: (319) 335-6933
Mentor: Paul McCray, MD
Undergraduate Institution: University of Iowa
Year Entered Into Program: 2013
I am investigating the use of viral vectors as delivery vehicles as a gene therapy approach for cystic fibrosis. Cystic fibrosis (CF) is a common autosomal recessive genetic disorder caused by a mutant cystic fibrosis transmembrane conductance regulator (CFTR) gene, an anion channel responsible for salt and water transport in epithelial cells across the airway surface. CF disease is characterized by chronic bacterial infection and inflammation due to host defense defects, and patients typically die of lung disease that begins early in childhood. As a single gene disorder, CF is a strong candidate for gene therapy. Complementation of the CFTR anion channel in CF airway cells can restore ion exchange across the epithelial surface, and therefore has potential to correct the disease. The goal of my thesis work is to deliver CFTR to airway epithelia and rescue CFTR function using integrating non-viral and viral vectors such as hybrid piggyBac/adenovirus, hybrid piggyBac/adeno-associated virus (AAV) and lentivirus. Here at the University of Iowa, we have the opportunity to perform these studies in the CF pig, a large animal model that recapitulates lung disease similar to humans.
The big-picture question that I am seeking to address is: will CFTR gene transfer
to airway epithelia by an integrating vector efficiently and persistently
correct the phenotypes associated with CF disease? The aim of this work is to
optimize viral vectors to improve transgene delivery. Data from these studies
will advance the field of gene therapy and potentially advance to clinical
AL, Abou Alaiwa MH, Shah VS, Bouzek DC, Stroik MR, Powers LS. Gansemer ND,
Meyerholz DK, Welsh MJ, Sinn PL, McCray PB. Lentiviral-mediated
phenotypic correction of cystic fibrosis pigs. In submission.
AL, McCray PB, Sinn, PL. Integrating
viral and nonviral vectors for cystic fibrosis gene therapy in the airways.
In: Cystic Fibrosis in the Light of New Research. Dennis Wat (Ed.) Rijeka,
Croatia: InTech. (2015)10.5772/60977.
AL, Singh B, Sinn PL. Hybrid nonviral/viral vector systems for
improved DNA transposon in vivo delivery.
Molecular Therapy. (2015) 10.1038/mt.2014.254.
X, Burnight ER, Cooney AL, Malani N, Brady T, Sander JD, Staber J, Wheelan SJ,
Joung JK, McCray PB Jr, Bushman FD, Sinn PL, Craig NL. piggyBac
transposase tools for genome engineering.
PNAS. (2013) 110(25):E2279-87.
PL, Cooney AL, Oakland M, Dylla DE, Wallen TJ, Pezzulo AA, Chang EH, McCray PB
vector gene transfer to porcine airways.
Mol Ther Nucleic Acids. (2012)
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