Abstract
Polyglutamine (polyQ) diseases, including Huntington’s disease, are a group of late-onset progressive neurological disorders caused by CAG repeat expansions. Although recently, many studies have investigated the pathological features and development of polyQ diseases, many questions remain unanswered. The advancement of new gene-editing technologies, especially the CRISPR-Cas9 technique, has undeniable value for the generation of relevant polyQ models, which substantially support the research process. Here, we review how these tools have been used to correct disease-causing mutations or create isogenic cell lines with different numbers of CAG repeats. We characterize various cellular models such as HEK 293 cells, patient-derived fibroblasts, human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs) and animal models generated with the use of genome-editing technology.
Highlights
Polyglutamine diseases belong to a group of progressive neurodegenerative disorders
The polyQ expansions are fundamental to nine genetic neurological diseases, namely Huntington’s disease (HD), spinocerebellar ataxias (SCAs) (SCA1, SCA2, SCA3, SCA6, SCA7 and SCA17), dentatorubral-pallidoluysian atrophy (DRPLA) and spinobulbar muscular atrophy (SBMA) [1,2,3]
The application of the CRISPR system has been further extended by the use of other effector nucleases such as the Cas12a protein or by using modified nucleases such as Cas9 nickase (Cas9n), which only cleaves one strand at the target site, or catalytically-dead Cas9, which loses its nuclease activity but maintains the ability to bind to the sequence targeted by guide RNA (gRNA) [66,73,74]
Summary
Polyglutamine (polyQ) diseases belong to a group of progressive neurodegenerative disorders. Nuclease-based gene-editing methods such as meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas technology have significantly contributed to advances in disease modeling and augmented a variety of scientific research. Since their invention, genome-editing tools have become increasingly popular due to their ability to directly change DNA sequences and alter gene expression efficiently [40,41]. Application of modern genome-editing methods and development of new, more relevant models valuably contributes to improving our knowledge of polyQ diseases and lays a promising foundation for future therapeutic strategies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
