Abstract

The development of targeted therapeutics for rare neurodevelopmental disorders (NDDs) faces significant challenges due to the scarcity of subjects and the difficulty of obtaining human neural cells. Here, we illustrate a rapid, simple protocol by which patient derived cells can be reprogrammed to induced pluripotent stem cells (iPSCs) using an episomal vector and differentiated into neurons. Using this platform enables patient somatic cells to be converted to physiologically active neurons in less than two months with minimal labor. This platform includes a method to combine somatic cell reprogramming with CRISPR/Cas9 gene editing at single cell resolution, which enables the concurrent development of clonal knockout or knock-in models that can be used as isogenic control lines. This platform reduces the logistical barrier for using iPSC technology, allows for the development of appropriate control lines for use in rare neurodevelopmental disease research, and establishes a fundamental component to targeted therapeutics and precision medicine. Stem Cells Translational Medicine 2017;6:886–896

Details

Title
A Rapid Pipeline to Model Rare Neurodevelopmental Disorders with Simultaneous CRISPR/Cas9 Gene Editing
Author
Bell, Scott 1 ; Peng, Huashan 1 ; Crapper, Liam 1 ; Kolobova, Ilaria 1 ; Maussion, Gilles 1 ; Vasuta, Cristina 1 ; Yerko, Volodymyr 1 ; Tak Pan Wong 2 ; Ernst, Carl 3 

 McGill Group for Suicide Studies, Douglas Hospital Research Institute, Montreal, Quebec, Canada 
 Departments of Psychiatry, McGill University, Montreal, Quebec, Canada 
 McGill Group for Suicide Studies, Douglas Hospital Research Institute, Montreal, Quebec, Canada; Departments of Psychiatry, McGill University, Montreal, Quebec, Canada; Human Genetics, McGill University, Montreal, Quebec, Canada 
Pages
886-896
Section
Translational Research Articles and Reviews
Publication year
2017
Publication date
Mar 2017
Publisher
Oxford University Press
ISSN
21576564
e-ISSN
21576580
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2290230222
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.