Generation of isogenic pluripotent stem cells differing exclusively at two early onset parkinson point mutations

Frank Soldner, Josée Laganière, Albert W. Cheng, Dirk Hockemeyer, Qing Gao, Raaji Alagappan, Vikram Khurana, Lawrence I. Golbe, Richard H. Myers, Susan Lindquist, Lei Zhang, Dmitry Guschin, Lauren K. Fong, B. Joseph Vu, Xiangdong Meng, Fyodor D. Urnov, Edward J. Rebar, Philip D. Gregory, H. Steve Zhang, Rudolf Jaenisch

Research output: Contribution to journalArticlepeer-review

612 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)318-331
Number of pages14
Issue number2
StatePublished - Jul 22 2011

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


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