Patrick Sinn, Ph.D. (Associate Member) Assoc. Research Sci., Dept. of Pediatrics, University of Iowa
Research Interest
The primary goal of Dr. Sinn's research is to develop integrating vector systems for the treatment of inherited diseases such as Cystic Fibrosis (CF). Current main areas of focus include: 1) maximizing transduction efficiency in epithelial cells of the airway; 2) assessing host immune responses to transduction by lentiviral vectors; and 3) improving lentivirus-mediated gene transfer safety through site-restricted integration. To improve the transduction efficiency of lentiviral vectors, he has performed extensive screening of viral envelopes to identify those compatible with the vector that confer improved delivery to the respiratory tract. In addition, he has identified vector formulations that increase the efficiency of vector delivery to the airways, such as viscoelastic gels. The group can obtain long-term gene expression in the respiratory tract of mice following a single application of the vector. Very little is known about the immunologic consequences of the administration of single or multiple doses of the lentiviral vector to the respiratory tract. Dr. Sinn is investigating the potential for enhancing gene expression through more than one application of the vector and evaluating host humoral and cellular responses. A potential problem with all integrating vector systems is the disruption of the function of an endogenous gene and perturbing host cell function. Ideally this could be avoided if the vector integration complex could be guided to a "safe site" in the genome. Dr. Sinn is also pursuing strategies to modify the integration properties of the lentiviral vector system to address this important vector safety issue.
Selected Publications:
Sinn PL, Goreham-Voss JD, Hickey MA, Chikkanna-Gowda CP, McCray PB Jr. Enhanced gene expression conferred by stepwise modification of a non-primate lentiviral vector. Hum Gene Ther. 2007; 18: 1244-1252.
Sinn PL, Burnight ER, Hickey MA, Blissard GW, McCray PB Jr. Persistent gene expression in mouse nasal epithelia following feline immunodeficiency virus-based vector gene transfer. J Virol. 2005; 79: 12818-12827.
Sinn PL, Burnight ER, Shen H, Fan H, McCray PB Jr. Inclusion of proviral flanking regions of the Jaagsiekte sheep retrovirus envelope glycoprotein markedly increases lentivirus vector pseudotyping efficiency. Mol Ther. 2005; 11: 460-469.
Sinn PL, Penisten AK, Burnight ER, Hickey MA, Williams G, McCoy DM, Mallampalli RK, McCray PB Jr. Gene transfer to respiratory epithelia with lentivirus pseudotyped with Jaagsiekte sheep retrovirus envelope glycoprotein. Hum Gene Ther. 2005; 16: 479-488.
