CRISPR/Cas9 Technology as an Emerging Tool for Targeting Amyotrophic Lateral Sclerosis (ALS)

Kruminis-Kaszkiel, Ewa; Juranek, Judyta K.; Maksymowicz, Wojciech; Wojtkiewicz, Joanna

doi:10.3390/ijms19030906

Cited by 22 publications

(29 citation statements)

References 67 publications

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“…Moreover, the potential of the novel genome editing tool based on the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (CRISPR/Cas9) has been recently explored for modeling neurodegenerative diseases which pathomechanisms that have not yet been fully uncovered, including ALS (Kruminis-Kaszkiel et al, 2018 ). Indeed, both a zebrafish (Armstrong et al, 2016 ) and a mouse (Liu et al, 2017 ) ALS models have been developed by using this genome engineering technology to introduce patients-specific mutations in genes associated to the disease.…”

Section: Discussionmentioning

confidence: 99%

Biochemical Properties of Human D-amino Acid Oxidase Variants and Their Potential Significance in Pathologies

Sacchi

Cappelletti

Murtas

2018

Front. Mol. Biosci.

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The stereoselective flavoenzyme D-amino acid oxidase (DAAO) catalyzes the oxidative deamination of neutral and polar D-amino acids producing the corresponding α-keto acids, ammonia, and hydrogen peroxide. Despite its peculiar and atypical substrates, DAAO is widespread expressed in most eukaryotic organisms. In mammals (and humans in particular), DAAO is involved in relevant physiological processes ranging from D-amino acid detoxification in kidney to neurotransmission in the central nervous system, where DAAO is responsible of the catabolism of D-serine, a key endogenous co-agonist of N-methyl-D-aspartate receptors. Recently, structural and functional studies have brought to the fore the distinctive biochemical properties of human DAAO (hDAAO). It appears to have evolved to allow a strict regulation of its activity, so that the enzyme can finely control the concentration of substrates (such as D-serine in the brain) without yielding to an excessive production of hydrogen peroxide, a potentially toxic reactive oxygen species (ROS). Indeed, dysregulation in D-serine metabolism, likely resulting from altered levels of hDAAO expression and activity, has been implicated in several pathologies, ranging from renal disease to neurological, neurodegenerative, and psychiatric disorders. Only one mutation in DAO gene was unequivocally associated to a human disease. However, several single nucleotide polymorphisms (SNPs) are reported in the database and the biochemical characterization of the corresponding recombinant hDAAO variants is of great interest for investigating the effect of mutations. Here we reviewed recently published data focusing on the modifications of the structural and functional properties induced by amino acid substitutions encoded by confirmed SNPs and on their effect on D-serine cellular levels. The potential significance of the different hDAAO variants in human pathologies will be also discussed.

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Section: Discussionmentioning

confidence: 99%

Biochemical Properties of Human D-amino Acid Oxidase Variants and Their Potential Significance in Pathologies

Sacchi

Cappelletti

Murtas

2018

Front. Mol. Biosci.

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“…One caveat of using the CRISPR-Cas9 system, regarding ALS therapeutics, lies in the potential off-target effects which must be addressed before clinical trials commence [51,52]. Despite, this short-coming, the use of CRISPR-Cas9 as a gene therapy platform should result in a smooth transition from an exploratory identification of candidate genes in animal studies to eventual clinical trials [52,53].…”

Section: Amyotrophic Lateral Sclerosis (Als) and Gene Therapy Using Tmentioning

confidence: 99%

“…Currently, the use of animal models to validate the efficacy and safety of CRISPR-Cas9 as a genetic tool has significantly improved our understanding of disease pathophysiology with significant support in the development of preventative and therapeutic strategies [53]. Novel models developed using the CRISPR-Cas9 system have resulted in a renaissance across fields, facilitating studies such as those modelling neurodegenerative disease through mutations in endogenous genes by significantly reducing the amount of time and effort of generating mutant mice strains [53,54]. To better understand ALS, the generation and use of animal model using the CRISPR-Cas9 system would expedite the development of potential therapeutic solution, since the condition is caused by an amalgamation of genetic and environmental factors [53].…”

Section: Amyotrophic Lateral Sclerosis (Als) and Gene Therapy Using Tmentioning

confidence: 99%

“…Novel models developed using the CRISPR-Cas9 system have resulted in a renaissance across fields, facilitating studies such as those modelling neurodegenerative disease through mutations in endogenous genes by significantly reducing the amount of time and effort of generating mutant mice strains [53,54]. To better understand ALS, the generation and use of animal model using the CRISPR-Cas9 system would expedite the development of potential therapeutic solution, since the condition is caused by an amalgamation of genetic and environmental factors [53]. The remaining cases of ALS are associated with mutations in various genes, such as in the fused/translocated liposarcoma (FUS) or the 43-kDa TAR DNA-binding protein (TARDBP) gene [53].…”

Section: Amyotrophic Lateral Sclerosis (Als) and Gene Therapy Using Tmentioning

confidence: 99%

“…In fact, in the C9ORF72-deficient mice model, CRISPR-Cas9 was used to develop murine pathogenic variants of ALS to mimic multiple-mutation in genes coding different domains of a single protein in human [53]. In the ALS zebrafish model developed by Armstrong et al, they used the CRISPR-Cas9 system to introduce point mutations in the TARDBP and FUS genes; providing evidence that the generation of human disease induced by point mutations can be imitated with knock-in lines developed by homology-directed repair (HDR) following CRISPR-Cas9 [53,55]. Remarkably, the CRISPR-Cas9 system was able to edit the endogenous gene, despite being expressed in a phylogenetically distant species [53,55], which saved time and effort as genomic integration in zebrafish can be evaluated within two days [53,55].…”

Section: Amyotrophic Lateral Sclerosis (Als) and Gene Therapy Using Tmentioning

confidence: 99%

See 2 more Smart Citations

The Impact of CRISPR-Cas9 on Age-related Disorders: From Pathology to Therapy

Caobi¹,

Dutta²,

Garbinski³

et al. 2020

Aging and disease

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With advances in medical technology, the number of people over the age of 60 is on the rise, and thus, increasing the prevalence of age-related pathologies within the aging population. Neurodegenerative disorders, cancers, metabolic and inflammatory diseases are some of the most prevalent age-related pathologies affecting the growing population. It is imperative that a new treatment to combat these pathologies be developed. Although, still in its infancy, the CRISPR-Cas9 system has become a potent gene-editing tool capable of correcting gene-mediated age-related pathology, and therefore ameliorating or eliminating disease symptoms. Deleting target genes using the CRISPR-Cas9 system or correcting for gene mutations may ameliorate many different neurodegenerative disorders detected in the aging population. Cancer cells targeted by the CRISPR-Cas9 system may result in an increased sensitivity to chemotherapeutics, lower proliferation, and higher cancer cell death. Finally, reducing gene targeting inflammatory molecules production through microRNA knockout holds promise as a therapeutic strategy for both arthritis and inflammation. Here we present a review based on how the expanding world of genome editing can be applied to disorders and diseases affecting the aging population.

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A Review: CRISPR Cas System and the Mechanism With an Inhibition of Binding of CRISPR Cas‐9

Hosen,

Nishat,

Soaib

et al. 2024

Nano Select

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CRISPR Cas system is a revolutionary and precise genome editing system that induces bacterial and archaeal adaptive immunity and already has shown several promising applications in the treatment of genetic diseases and detection of nucleic acid targets. It is a complex tool, comprising diverse effector proteins and guide RNA that can be applied to dissociate and modify genes in living organisms along with the in vitro process. The review concentrates on the advances accomplished from some recent years to 2023 for the emergence of predicting actions of Cas protein with the guide RNA (gRNA), playing a key role in genome editing. This review emphasizes the effect of DNA structure and chromosomal protein on Cas 9 binding with a distinct classification of Cas types. The relevance of this review is highlighted by the significance of the rapid development of wide study methods and their potential impacts on the efficiency of the CRISPR Cas system. We have analyzed recent kinds of literature in this work to integrate a deep learning way that contributes over the next time with some important discussion about viral resistance in eukaryotes along with some cancer treatment strategies, and crop improvement by the CRISPR Cas system.

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CRISPR/Cas9 Technology as an Emerging Tool for Targeting Amyotrophic Lateral Sclerosis (ALS)

Cited by 22 publications

References 67 publications

Biochemical Properties of Human D-amino Acid Oxidase Variants and Their Potential Significance in Pathologies

Biochemical Properties of Human D-amino Acid Oxidase Variants and Their Potential Significance in Pathologies

The Impact of CRISPR-Cas9 on Age-related Disorders: From Pathology to Therapy

A Review: CRISPR Cas System and the Mechanism With an Inhibition of Binding of CRISPR Cas‐9

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