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Patrick Sinn, Ph.D.

Portrait
Associate Professor of Pediatrics - Pulmonary Medicine
Associate Professor of Microbiology and Immunology
Faculty Director, Viral Vector Core

Contact Information

Lab
6318 PBDB
169 Newton Road
Iowa City, IA 52242
319-335-8190

Education

BA, Biology, University of Minnesota
PhD, Physiology and Biophysics, University of Iowa
Postdoctoral Fellow, Program in Gene Therapy, University of Iowa

Research Summary

Engineering novel gene delivery tools

The aim of gene therapy vector development for life-long genetic diseases such as CF is to create a vehicle with the ability to efficiently, safely, and persistently express a transgene in the appropriate cell types. There are multiple viral based vectors for delivering genes to the airways. Each system has its pros and cons. Non-viral vectors, such as DNA transposons provide an expanded tool-set for gene transfer to cells. In particular, the recombinant DNA transposon, piggyBac, achieves efficient genomic integration of a transgene when transposase is supplied in trans. Recombinant piggyBac transposon and transposase are typically co-delivered by plasmid transfection; however, the greatest barrier to any plasmid based vector is inefficient delivery. We have shown the potential for using viral vectors (both Ad and AAV) to deliver piggyBac components to cells and achieve transposase mediated genomic integration of the transposon. A hybrid piggyBac/viral vector has the combined advantage of a very efficient gene transfer reagent with life-long expression. This novel hybrid vector system provides a valuable additional tool for in vivo gene transfer.

Measles virus (MV) entry and spread in airway cells

Despite an effective vaccine, MV remains a world wide health burden and is resurging in the US. Medical texts teach that MV initially infects and replicates locally in respiratory cells and subsequently spreads to the lymphatic system. However, we challenged this dogma. Prior to our study in 2002, MV was thought to enter the apical surface of airway epithelia. By using well-differentiated primary cultures of airway epithelia from human donors, we were the first to demonstrate that MV has an overwhelming preference for the basolateral surface. At the time, this result was very unexpected. We subsequently demonstrated in our 2008 and 2011 publications that MV uses an epithelial specific cellular receptor, Nectin-4, to enter airway cells. Another important observation from our 2002 study was MV infection of primary airway cells is non-cytopathic, as is typically observed with MV infected immortalized cells. MV infected airway cells form infectious centers that retain individual nuclei, plasma membranes, and transepithelial resistance. One of the critical challenges for the field of cell-to-cell transmission is a model system that mirrors how viruses actually spread in living organisms. Primary airway cells are the best models for studying cell-to-cell transmission of MV in epithelia. There are so many questions that wait to be answered about an extremely contagious human virus.