ZIYING
YAN, Ph.D.
Assistant Research Scientist
ziying-yan@uiowa.edu
Training
B.S., Sun Yatsen (Zhongshan) University, 1986 (Biochemistry)
M.S., Sun Yatsen (Zhongshan) University, 1989 (Biochemistry)
Ph.D., Chinese Academy of Preventive Medicine, 1995 (Molecular Virology)
Research Interests:
Adeno-associated viral (AAV) vectors have demonstrated considerable
promise for gene therapy of inherited diseases. However, with a packaging
limitation of <5kb, applications have been limited to relatively small
disease genes. AAV has been demonstrated to form circular intermediates
following transduction in muscle and cell lines, and their episomal persistence
correlates to long-term transgene expression. Those circular viral genomes
appear to originate through a monomeric circularization process leading
to head to tail AAV circular genomes. However, over time, there is a decline
in monomer circular intermediates in favor of high molecular weight concatamers.
My ongoing research is focused on characterizing the potential mechanisms
involved in the formation of rAAV circular intermediates, especially of
the circular concatamers. Based on findings that AAV genomes undergo intermolecular
circular concatamerization following transduction in muscle, we have developed
a paradigm to increase the size of delivered transgenes with this vector
through trans-splicing between two independent vectors co-administered
to the same tissue. We have recently demonstrated that therapeutic levels
of protein expression can be generated from these trans-splicing AAV vectors,
indicating their application in a wider variety of diseases.
Selected Publications:
ZIYING YAN, R. Zak, G. Luxton, T. Ritchie, U Bantel-Schaal and JF Engelhardt:
Ubiquitination of both Adeno-Associated Virus Type 2 and 5 capsid proteins
affects the transduction efficiency of recombinant vectors. Journal
of Virology, 76(5): in press, 2002.
D. Duan, ZIYING YAN, Y Yue, W Ding and JF Engelhardt: Enhancement of Muscle Gene Delivery with Pseudotyped Adeno-Associated Virus Type 5 Correlates with Myoblast Differentiation. Journal of Virology, 75(16): 7662-7671, 2001.
D. Duan, Y. Yue, ZIYING YAN, and JF Engelhardt: Endosomal Proceding is a Major Limiting Step in the Adeno-Associated Virus-mediated Gene Transfer to Polarized Airway Epithelia. Journal of Clinical Investigation, 105(11), 1573-1587, 2000.
D. Duan, Y. Yue, ZIYING YAN, and JF Engelhardt: Novel Approach to Enhance Recombinant AAV-mediated Gene Expression Through Intermolecular Cis activation. Nature Medicine, 6(5): 595-598, 2000.
ZIYING YAN, Y Zhang, D Duan and JF Engelhardt: Trans-splicing viral vectors
expand the utility of AAV for gene therapy. Proc Natl Acad Sci U S A 97:6716-6721,
2000.
D Duan, ZIYING YAN, Y Yue and JF Engelhardt: Structural analysis of AAV
transduction circular intermediates. Virology, 261: 8-14, 1999.
ZIYING YAN, J. Qiao, H Gong and Yunde Hou: A novel liver directed gene
delivery system with an autonomously replicating vector specially expression
in AFP positive hepatoma cells. Science in China (English version), Series
C, 41(1): 80~85, 1998
Y.-L. Shu, X.-B. Wu, Huiyu Gong, Yunde Hou and ZIYING YAN. A defective
Herpes virus stock produced by an AAV- HSV-1 amplicon chimeric plasmid
for packaging recombinant Adeno-associated virus vector. Science in China
(Chinese version), 28(5): 1~5, 1998.
ZIYING YAN, E.-M. Yao, T. Zhang, Y.-L. Shu and Yunde Hou: A novel package
system based on an EBV replicon vector for producing high titer recombinant
AAV vector. Chinese Science Bulletin (English version), 42(20): 1741~1744,
1997.