Gene correction of an expanded CAG repeat in induced pluripotent stem cell-derived neural stem cells using adeno-associated virus-mediated targeting

Daniel Poppe, Peter Breuer, Jonas Doerr, Johannes Jungverdorben, Michael Peitz, Oliver Brüstle, Philipp Koch

Research output: Contribution to conferencePoster

Abstract

Considering the genetic variations of human individuals, isogenic induced
pluripotent stem (iPS) cell lines are currently discussed as the most appropriate
controls for IPS cell-based disease models. Here we present the efficient gene
correction of a disease-causing allele in human iPSC-derived neuroepithelial
stem (lt-NES) cells generated from a patient with Machado-Joseph Disease
(MJD). In MJD, the expansion of a polyglutamine-encoding CAG motif in the
ATXN3 gene induces the formation of ATXN3-containing aggregates and
neurodegeneration. To exchange the expanded exon by the non-expanded
allele of the same patient, we used the ability of recombinant adeno-associated
viral vectors to target homologous loci with high fidelity. Neurons derived from
targeted lt-NES cells did no longer show disease-specific phenotypic changes
such as activity-dependent formation of ATXN3-containing aggregates. Our
data suggest that AAV-mediated gene correction could represent a fast and
efficient approach to generate isogenic controls in iPSC-based disease
modeling.
Original languageEnglish
Pages1
Number of pages1
Publication statusPublished - 22 Nov 2013
EventCell Symposia: Using Stem Cells to Model and Treat Human Disease - Cedars-Sinai Medical Center, Los Angeles, United States
Duration: 21 Nov 201323 Nov 2013
http://www.cell-symposia.com/stemcells-modelingtreatingdisease-2013/

Conference

ConferenceCell Symposia: Using Stem Cells to Model and Treat Human Disease
CountryUnited States
CityLos Angeles
Period21/11/1323/11/13
Internet address

Fingerprint

Dive into the research topics of 'Gene correction of an expanded CAG repeat in induced pluripotent stem cell-derived neural stem cells using adeno-associated virus-mediated targeting'. Together they form a unique fingerprint.

Cite this