Nature Communications (Oct 2022)
CRISPR/Cas9-mediated excision of ALS/FTD-causing hexanucleotide repeat expansion in C9ORF72 rescues major disease mechanisms in vivo and in vitro
- Katharina E. Meijboom,
- Abbas Abdallah,
- Nicholas P. Fordham,
- Hiroko Nagase,
- Tomás Rodriguez,
- Carolyn Kraus,
- Tania F. Gendron,
- Gopinath Krishnan,
- Rustam Esanov,
- Nadja S. Andrade,
- Matthew J. Rybin,
- Melina Ramic,
- Zachary D. Stephens,
- Alireza Edraki,
- Meghan T. Blackwood,
- Aydan Kahriman,
- Nils Henninger,
- Jean-Pierre A. Kocher,
- Michael Benatar,
- Michael H. Brodsky,
- Leonard Petrucelli,
- Fen-Biao Gao,
- Erik J. Sontheimer,
- Robert H. Brown,
- Zane Zeier,
- Christian Mueller
Affiliations
- Katharina E. Meijboom
- Horae Gene Therapy Center, University of Massachusetts Medical School
- Abbas Abdallah
- Horae Gene Therapy Center, University of Massachusetts Medical School
- Nicholas P. Fordham
- Horae Gene Therapy Center, University of Massachusetts Medical School
- Hiroko Nagase
- Horae Gene Therapy Center, University of Massachusetts Medical School
- Tomás Rodriguez
- RNA Therapeutics Institute and Program in Molecular Medicine, University of Massachusetts Medical School
- Carolyn Kraus
- RNA Therapeutics Institute and Program in Molecular Medicine, University of Massachusetts Medical School
- Tania F. Gendron
- Department of Neuroscience, Mayo Clinic
- Gopinath Krishnan
- Department of Neurology, University of Massachusetts Medical School
- Rustam Esanov
- Department of Psychiatry & Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine
- Nadja S. Andrade
- Department of Psychiatry & Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine
- Matthew J. Rybin
- Department of Psychiatry & Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine
- Melina Ramic
- Department of Psychiatry & Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine
- Zachary D. Stephens
- Department of Quantitative Health Sciences. Mayo Clinic
- Alireza Edraki
- RNA Therapeutics Institute and Program in Molecular Medicine, University of Massachusetts Medical School
- Meghan T. Blackwood
- Horae Gene Therapy Center, University of Massachusetts Medical School
- Aydan Kahriman
- Department of Neurology, University of Massachusetts Medical School
- Nils Henninger
- Department of Neurology, University of Massachusetts Medical School
- Jean-Pierre A. Kocher
- Department of Quantitative Health Sciences. Mayo Clinic
- Michael Benatar
- Department of Neurology, University of Miami Miller School of Medicine
- Michael H. Brodsky
- Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School
- Leonard Petrucelli
- Department of Neuroscience, Mayo Clinic
- Fen-Biao Gao
- Department of Neurology, University of Massachusetts Medical School
- Erik J. Sontheimer
- RNA Therapeutics Institute and Program in Molecular Medicine, University of Massachusetts Medical School
- Robert H. Brown
- Department of Neurology, University of Massachusetts Medical School
- Zane Zeier
- Department of Psychiatry & Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine
- Christian Mueller
- Horae Gene Therapy Center, University of Massachusetts Medical School
- DOI
- https://doi.org/10.1038/s41467-022-33332-7
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 17
Abstract
A hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of ALS and FTD. Here, the authors demonstrate CRISPR/Cas9 excision of the expansion results in a rescue of disease mechanisms in vivo and in vitro.
