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Review
. 2023 Mar;60(3):1486-1498.
doi: 10.1007/s12035-022-03150-5. Epub 2022 Dec 9.

CRISPR/Cas9 Mediated Therapeutic Approach in Huntington's Disease

Suleyman Serdar Alkanli  1   2 , Nevra Alkanli  3 , Arzu Ay  4 , Isil Albeniz  5
Affiliations
Review

CRISPR/Cas9 Mediated Therapeutic Approach in Huntington's Disease

Suleyman Serdar Alkanli et al. Mol Neurobiol. 2023 Mar.

Abstract

The pathogenic mechanisms of these diseases must be well understood for the treatment of neurological disorders such as Huntington's disease. Huntington's Disease (HD), a dominant and neurodegenerative disease, is characterized by the CAG re-expansion that occurs in the gene encoding the polyglutamine-expanded mutant Huntingtin (mHTT) protein. Genome editing approaches include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats/Caspase 9 (CRISPR/Cas9) systems. CRISPR/Cas9 technology allows effective gene editing in different cell types and organisms. Through these systems are created isogenic control of human origin induced pluripotent stem cells (iPSCs). In human and mouse models, HD-iPSC lines can be continuously corrected using these systems. HD-iPSCs can be corrected through the CRISPR/Cas9 system and the cut-and-paste mechanism using isogenic control iPSCs. This mechanism is a piggyBac transposon-based selection system that can effectively switch between vectors and chromosomes. In studies conducted, it has been determined that in neural cells derived from HD-iPSC, there are isogenic controls as corrected lines recovered from phenotypic abnormalities and gene expression changes. It has been determined that trinucleotide repeat disorders occurring in HD can be cured by single-guide RNA (sgRNA) and normal exogenous DNA restoration, known as the single guideline RNA specific to Cas9. The purpose of this review in addition to give general information about HD, a neurodegenerative disorder is to explained the role of CRISPR/Cas9 system with iPSCs in HD treatment.

Keywords: CRISPR/Cas9; Genome Editing Systems; Huntington’s Disease; Isogenic Cell Lines; Neurodegenerative Disorders; iPSC.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Current treatment approaches for HD [19]
Fig. 2
Fig. 2
ZFN, TALEN and CRISPR Genome editing approaches [34]
Fig. 3
Fig. 3
CRISPR/Cas9 approach to reduction and permanent inactivation of HD [43]
Fig. 4
Fig. 4
DNA repair mechanisms in gene editing systems [49]
Fig. 5
Fig. 5
CRISPR gene editing with human iPSCs [54]
See this image and copyright information in PMC

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