Ziying Yan, Ph.D. (Associate Member)
Res. Assoc. Prof., Anatomy & Cell Biology, University of Iowa

http://elab.genetics.uiowa.edu/MEMBERPAGES/Ziying/Ziyningyanpage.htm

Research Interest    

Dr. Yan's research interests pertain to the molecular biology of adeno-associate virus (AAV) and the development of recombinant AAV as a vector for application in gene therapy. Dr. Yan?s research focuses on the virus-host cell interactions that facilitate conversion of the viral genome and intracellular trafficking of the virion. Dr. Yan is particularly interested in the roles that AAV inverted terminal repeats (ITR) play in the circularization and concatamerization of the rAAV genome. He has developed a new form of hybrid rAAV vector that features serotype-2 and -5 ITR-containing genomes. This hybrid vector positively influences the directionality of intermolecular recombination by the viral genome and significantly improves the efficacy of the AAV trans-splicing dual vector system, which doubles the AAV packaging capacity such that it is suitable for the delivery of large genes. Another ongoing project is focused on determining how the cellular proteasome system and the ubiquitination of viral particles contribute to the intracellular trafficking of AAV. Dr. Yan also utilizes rAAV as a targeting vector to generate genetically modified cell lines for use in human disease modeling. A notable achievement in this regard is his recent use of the AAV-mediated gene targeting technique to disrupt the CFTR gene in ferret primary fibroblasts, cells that have now been used to successfully create a CFTR knock-out ferret by cloning via a somatic cell nuclear transfer approach.

Selected Publications:

Sun, X*., Yan, Z*., Yi, Y., Li, Z., Lei, D., Rogers, C.S., Chen, J., Zhang, Y., Welsh, M.J., Leno, G.H., and Engelhardt, J.F. 2008. Adeno-associated virus-targeted disruption of the CFTR gene in cloned ferrets. J Clin Invest. (In press, e-print) *equal contribution first author.

Yan Z, Lei-Butters DC, Zhang Y, Zak R, Engelhardt JF. Hybrid adeno-associated virus bearing nonhomologous inverted terminal repeats enhances dual-vector reconstruction of minigenes in vivo. Hum Gene Ther. 2007 (1):81-7.

Yan Z, Lei-Butters DC, Liu X, Zhang Y, Zhang L, Luo M, Zak R, Engelhardt JF. Unique biologic properties of recombinant AAV1 transduction in polarized human airway epithelia. J Biol Chem. 2006, 281(40):29684-92.

Yan Z, Zak R, Zhang Y, Engelhardt JF. Inverted terminal repeat sequences are important for intermolecular recombination and circularization of adeno-associated virus genomes. J Virol. 2005 Jan;79(1):364-79.

Publications from Gene Therapy Center

Publications from PubMed