Anton McCaffrey, Ph.D. (Full Member)
Assistant Professor, University of Iowa

http://www.int-med.uiowa.edu/Divisions/ID/Directory/AntonMcCaffrey.html

Research Interest    

The Role of MicroRNAs During Chronic Hepatitis C Virus (HCV) Infection
Dr. McCaffrey's lab has conducted high-throughput Q-PCR expression profiling of microRNAs in needle biopsies from chronically infected HCV patients and have identified a number of microRNAs that are altered during infection. They use a variety of cell culture and animal models to assess whether these microRNAs are induced by the virus to its advantage, induced as part the host damage response or if they are induced as part of the host anti-viral response.

The Role of MicroRNAs During Liver Regeneration
Again using high-throughput Q-PCR, Dr. McCaffrey's lab has identified microRNAs that are differentially expressed during liver regeneration. We use reporter assays to identify targets mRNAs of these microRNAs.

RNA Interference (RNAi) Therapeutics Targeting Hepatitis B Virus (HBV)
Using rational approaches, Dr. McCaffrey and his colleagues have developed highly potent RNAi targeting HBV. They use adeno-associated virus vectors (AAV) to deliver RNAi to HBV transgenic mice. They observe long term silencing of HBV with these vectors.

Zinc-finger Nucleases Targeting HBV
Dr. McCaffrey's lab builds designer restriction enzymes that recognize sequences in the HBV genome and cleave them. These enzymes are called zinc-finger nucleases (ZFNs). In cultured cells, they have shown that these ZFNs cut model HBV substrates. These cut DNAs are repaired by non-homologous end joining which introduces insertions and deletions that should be deleterious to the virus. They are currently developing viral vectors expressing these ZFN for testing in mouse models of HBV.

Selected Publications:

McCaffrey, A.P., Nakai, H., Pandey, K., Huang, H., Xu, H., Salazar, F.H., Marion, P.L. and Kay, M.A.
Inhibition of Hepatitis B Virus in Mice by RNA Interference. Nature Biotechnology 21, 639-44. 2003.

McCaffrey, A.P., Meuse, L., Karimi, M., Contag, C.H., and Kay, M.A. 2003. A Potent and Specific Morpholino Antisense Inhibitor of Hepatitis C Translation in Mice. Hepatology 38:503-508.

Layzer, J., McCafferey, A.P., Tanner, A., Kay M.A. and Sullenger, B.A. In Vivo Activity of Nuclease-Resistant siRNAs. RNA 10, 766-71. 2004.

Marquez, R.T., and McCaffrey, A.P. Advances in MicroRNAs: Implications for Gene Therapists. Hum Gene Ther. 2007. (In Press)

Publications from PubMed