Download Protein-based cellular alchemy for personalized medicine: A case

Protein-based cellular alchemy for personalized
medicine: A case for Parkinson’s disease
Kwang-Soo Kim
Affiliation: Molecular Neurobiology, McLean Hospital/Harvard Medical School
Address: MRC216, 115 Mill Street, Belmont, MA 02478, USA
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The induced pluripotent stem cell (iPSC) technology pioneered by Yamanaka and his
colleagues in 2006 has ignited an explosion of scientific and public interest because these cells
can potentially offer an ideal cell source by providing patient- and disease-specific cells to study
and treat numerous human diseases. However, widely established methods to generate iPSCs
require the use of viral and/or genetic materials that likely integrate into the chromosomal DNAs
with unknown genetic changes. Indeed, recent evidence demonstrated that viral-based iPS cells
compromise genomic integrity and exhibit abnormal phenotypes. Thus, to realize the
therapeutic and biomedical potentials of iPSCs, it is critical to develop reprogramming methods
that can avoid or minimize these potential abnormalities. As a potential approach, we attempted
to generate iPSCs without the use of viruses or DNA transfection by directly delivering four
reprogramming proteins (Oct4, Sox2, Klf4, and c-Myc) fused with a cell penetrating peptide. We
also characterized these protein-based iPSCs along with virus-based iPSCs for their molecular
and differentiation properties. This presentation will discuss current limitations as well as the
potential of protein-based iPSC reprogramming with the long-term goal to use them for eventual
personalized medicine, using the case of Parkinson’ disease as a model system.
Recent relevant publications
Kim, D., Kim, C.-H., Moon, J., Chung, Y.-G., Chang, M.-Y., Han, B.-S., Ko, S., Yang, E., Cha,
K.Y., Lanza, R., Kim, K.S. (2009). Generation of Human Induced Pluripotent Stem Cells by
Direct Delivery of Reprogramming Proteins. Cell Stem Cell 4(6):472-6. (selected as one of
2009 Research Highlights by Nature 2009, 462:960).
Chung, S., Leung, A., Hong, S.H., Chang, M.Y., Pruszak, J., Han, B.-S., Isacson, O. and Kim,
K.S. (2009) Wnt1 and Lmx1a form a novel autoregulatory loop and critically regulate
midbrain dopaminergic development at multiple steps. Cell Stem Cell 5:646-58.
Rhee, Y.-H., Ko, J.-Y., Chang, M.-Y., Yi, S.-H., Kim, D., Kim, C.-H., Shim, J.-W., Jo, A.-Y., Kim,
B.-W., Lee, H., Lee, S.-H., Suh, W., Park, C.-H., Koh, H.-C., Lee, Lee, Y.-S., Lanza, R., Kim,
K.S.* and Lee, S.-H.* (*co-corresponding authors) (2011) Protein-based human iPS cells
efficiently generate functional dopamine neurons without abnormal phenotypes associated
with genome integration. J. Clin. Invest. 121(6):2326-35. Epub 2011 May 16. (featured in
Nature Review Neurology, 2011, 7:357).
Chung, S., Moon, J.-I., Leung, A., Aldrich, D., Lukianov, S., Kitayama, Y., Park, S., Li, Y.,
Bolshakov, V.Y., Lamonerie, R., and Kim, K.S. (2011) ES cell-derived renewable and
functional midbrain dopaminergic progenitors P.N.A.S. 108(23):9703-8. Epub 2011 May 23.
Kim, K.S. (2011) Converting human skin cells to neurons: A new tool to study and treat brain
disorders? Cell Stem Cell, 9:179-181.
Vasudevan, A., Won, C., Li, S., Erdelyi, F., Szabo, G., and Kim, K.S. (2012). Dopaminergic
Neurons Modulate GABA Neuron Migration in the Embryonic Midbrain. Development, 139:
3136-41. (PMC3413160)