Generation of Isogenic Pluripotent Stem Cells Differing Exclusively at Two Early Onset Parkinson Point Mutations
Name
Soldner-2011-Generation of Isogen.pdf
Size
2.86 MB
Format
Adobe PDF
Checksum (MD5)
1bef01b59d9a6fbec6460c6471b1a484
Author(s)
Soldner, Frank
Hockemeyer, Dirk
Gao, Qing
Alagappan, Raaji
Khurana, Vikram
Golbe, Lawrence I.
Myers, Richard H.
Lindquist, Susan
Guschin, Dmitry
Fong, Lauren K.
Date Issued
July 2011
Journal
Cell
Publisher
Elsevier
Citation
Soldner, Frank, Josee Laganiere, Albert W. Cheng, Dirk Hockemeyer, Qing Gao, Raaji Alagappan, Vikram Khurana, et al. “Generation of Isogenic Pluripotent Stem Cells Differing Exclusively at Two Early Onset Parkinson Point Mutations.” Cell 146, no. 2 (July 2011): 318–331. © 2011 Elsevier Inc.
Version
Final published version
Abstract
Patient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells provide a unique tool for the study of human disease, as well as a promising source for cell replacement therapies. One crucial limitation has been the inability to perform experiments under genetically defined conditions. This is particularly relevant for late age onset disorders in which in vitro phenotypes are predicted to be subtle and susceptible to significant effects of genetic background variations. By combining zinc finger nuclease (ZFN)-mediated genome editing and iPSC technology, we provide a generally applicable solution to this problem, generating sets of isogenic disease and control human pluripotent stem cells that differ exclusively at either of two susceptibility variants for Parkinson's disease by modifying the underlying point mutations in the α-synuclein gene. The robust capability to genetically correct disease-causing point mutations in patient-derived hiPSCs represents significant progress for basic biomedical research and an advance toward hiPSC-based cell replacement therapies.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2011.06.019
