Genome Editing for CNS Disorders

Duarte, Fábio Teixeira; Déglon, Nicole

doi:10.3389/fnins.2020.579062

Cited by 22 publications

(18 citation statements)

References 179 publications

(211 reference statements)

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“…Genome editing enables insertion, deletion, or replacement of nucleotides, but also modulation of gene expression and epigenetic editing (Duarte and Déglon, 2020). In monogenetic CNS diseases, a disease-causing mutation leading to either LoF or GoTF can be corrected by targeted editing of the specific mutation to restore a healthy phenotype.…”

Section: Genome Editingmentioning

confidence: 99%

“…Recently, the CRISPR/Cas-based genome editing has prevailed over the ZFNs and TALENs since they are easier to engineer to recognize unique sequences. The DNA-binding specificity of ZFNs and TALENs is dependent on protein-DNA interactions whereas the CRISPR/Cas is provided by the sgRNAs, which are simpler and less expensive to design (Duarte and Déglon, 2020).…”

Section: Genome Editingmentioning

confidence: 99%

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Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord

Jensen

Gøtzsche

Woldbye

2021

Front. Mol. Neurosci.

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In recent years, gene therapy has been raising hopes toward viable treatment strategies for rare genetic diseases for which there has been almost exclusively supportive treatment. We here review this progress at the pre-clinical and clinical trial levels as well as market approvals within diseases that specifically affect the brain and spinal cord, including degenerative, developmental, lysosomal storage, and metabolic disorders. The field reached an unprecedented milestone when Zolgensma® (onasemnogene abeparvovec) was approved by the FDA and EMA for in vivo adeno-associated virus-mediated gene replacement therapy for spinal muscular atrophy. Shortly after EMA approved Libmeldy®, an ex vivo gene therapy with lentivirus vector-transduced autologous CD34-positive stem cells, for treatment of metachromatic leukodystrophy. These successes could be the first of many more new gene therapies in development that mostly target loss-of-function mutation diseases with gene replacement (e.g., Batten disease, mucopolysaccharidoses, gangliosidoses) or, less frequently, gain-of-toxic-function mutation diseases by gene therapeutic silencing of pathologic genes (e.g., amyotrophic lateral sclerosis, Huntington's disease). In addition, the use of genome editing as a gene therapy is being explored for some diseases, but this has so far only reached clinical testing in the treatment of mucopolysaccharidoses. Based on the large number of planned, ongoing, and completed clinical trials for rare genetic central nervous system diseases, it can be expected that several novel gene therapies will be approved and become available within the near future. Essential for this to happen is the in depth characterization of short- and long-term effects, safety aspects, and pharmacodynamics of the applied gene therapy platforms.

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Section: Genome Editingmentioning

confidence: 99%

Section: Genome Editingmentioning

confidence: 99%

Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord

Jensen

Gøtzsche

Woldbye

2021

Front. Mol. Neurosci.

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“…The advancement in precise and sophisticated genome editing tools has paved the way in drug discovery, genetic diagnosis, and even basic biology techniques which were all far approachable. The key features in editing involves recognition of a unique target sequence within the DNA-binding domain and secondly to induce precise modification in genetic or epigenetic level using an effector element [373].…”

Section: Crispr-cas System and Other Gene Editing Technologymentioning

confidence: 99%

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases

et al. 2021

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The etiology of many neurological diseases affecting the central nervous system (CNS) is unknown and still needs more effective and specific therapeutic approaches. Gene therapy has a promising future in treating neurodegenerative disorders by correcting the genetic defects or by therapeutic protein delivery and is now an attraction for neurologists to treat brain disorders, like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, spinocerebellar ataxia, epilepsy, Huntington's disease, stroke, and spinal cord injury. Gene therapy allows the transgene induction, with a unique expression in cells' substrate. This article mainly focuses on the delivering modes of genetic materials in the CNS, which includes viral and non-viral vectors and their application in gene therapy. Despite the many clinical trials conducted so far, data have shown disappointing outcomes. The efforts done to improve outcomes, efficacy, and safety in the identification of targets in various neurological disorders are also discussed here. Adapting gene therapy as a new therapeutic approach for treating neurological disorders seems to be promising, with early detection and delivery of therapy before the neuron is lost, helping a lot the development of new therapeutic options to translate to the clinic.

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“…New directions are evolving in the Genome editing. This includes not only the insertion, deletion, or replacement of nu-cleotides, but also the modulation of gene expression and epigenetic editing (62) . Emerging technologies like CRISPR/Cas systems and others have extended genome manipulation boundaries and promoted genome editing techniques to the level of promising strategies for counteracting genetic diseases.…”

Section: Sli Gene-treatment Optionsmentioning

confidence: 99%

Specific Language Impairment Genes, Variants and Possible Gene-based Interventions

Eldesouki

2021

Suez Canal University Medical Journal

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Specific Language Impairment (SLI) is a communication neurodevelopmental disorder that manifests at the age of 3-5 years when a child lags his chronological speech development age by one year in the absence of medical, environmental, and psychological risk factors. SLI has been known to be highly heritable. Many studies have demonstrated different genes and loci to be implicated in SLI through linkage studies, the commonest of which were,

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Genome Editing for CNS Disorders

Cited by 22 publications

References 179 publications

Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord

Current and Future Prospects for Gene Therapy for Rare Genetic Diseases Affecting the Brain and Spinal Cord

Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases

Specific Language Impairment Genes, Variants and Possible Gene-based Interventions

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