Department of Internal Medicine
Infectious Diseases Faculty
Education:
B.A., University of California,
San Diego
Ph.D., University of Colorado,
Boulder
Residency:
Stanford University
Anton P. McCaffrey, Ph.D.
Assistant Professor
Laboratory Interests
RNA interference therapeutics targeting hepatitis B virus
Our previous studies have shown that hepatitis B virus (HBV) RNA interference (RNAi) can be effective at inhibiting HBV replication in mouse models. However, expression of too much RNAi can be toxic because it competes for the endogenous miRNA machinery. We use rational approaches to design more potent RNAi that functions at much lower doses. We are currently expressing this HBV RNAi from self-complementary adeno-associated virus serotype 8 (AAV8) vectors for testing in HBV transgenic mice.
Designing and constructing zinc-finger nucleases that recognize and cleave the genome of HBV
Current treatments for HBV are effective in only ~50 % of patients. This is in part because of the persistence of the HBV DNA genome. We have set out to design the first class of drugs that directly target the genome of a DNA virus for destruction. We build designer restriction enzymes, called zinc-finger nucleases (ZFNs), that specifically bind to HBV sequences and catalyze their cleavage in cells. We are currently testing this new type of therapeutic in mice.
The role of microRNAs in normal and pathogenic liver function
MiRNAs (miRNAs) are small regulatory RNAs that modulate gene expression by binding to the 3’ untranslated regions of mRNAs and causing translational inhibition or mRNA degradation. The McCaffrey lab studies miRNAs involved in normal liver functions as well as miRNAs involved in pathological processes. We utilize mouse models and also obtain human clinical samples through collaborations with hepatologists and transplant surgeons here at the University of Iowa.
Select Publications
- McCaffrey, A. P., Fawcett, P., Nakai, H., Ehrhardt, A., Pham, T.T., Pandey, K., Xu, H., Feuss, S., Storm, T., and Kay, M.A., Host Response to Helper Dependent Adenovirus and Adeno-associated Virus in Mouse Liver. Molecular Therapy (in press). 2008.
- Marquez RT, McCaffrey AP., Advances in microRNAs: implications for gene therapists. Human Gene Therapy, 19: 27-38, 2008.
- 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. Nat Biotechnol 21:639-644, 2003.
- McCaffrey, A.P., Meuse, L., Karimi, M. and Kay, M.A. Potent Morpholino Antisense Inhibitors of Hepatitis C Internal Ribosome Entry Site Translation in Mice. Hepatology 38:503-508, 2003.
- McCaffrey, A.P., Meuse, L., Pham, T.T. and Kay, M.A. RNA interference in adult mice. Nature 418:38-39, 2002.
Links of Interest