Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease
Recent advances in gene-editing technologies offer new opportunities for drug development to treat unmet medical needs in central nervous system (CNS) disorders including neurogenerative diseases of the aging brain. The adeno-associated virus (AAV) is a promising and most widely utilized vector for...
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Elsevier
2025-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253125001891 |
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| author | Boris Kantor Bernadette O'Donovan Ornit Chiba-Falek |
| author_facet | Boris Kantor Bernadette O'Donovan Ornit Chiba-Falek |
| author_sort | Boris Kantor |
| collection | DOAJ |
| description | Recent advances in gene-editing technologies offer new opportunities for drug development to treat unmet medical needs in central nervous system (CNS) disorders including neurogenerative diseases of the aging brain. The adeno-associated virus (AAV) is a promising and most widely utilized vector for gene therapy application including the CNS. AAV is characterized by high transduction efficiency in both dividing and non-dividing cells, low immunogenicity and toxicity, and exceptional tissue specificity. The development of clustered regularly interspaced short-palindromic repeat (CRISPR)-based technologies has revolutionized all aspects of modern sciences and created an innovative therapeutic toolkit with the potential to address a wide range of neurological diseases, including Alzheimer’s (AD) and Parkinson’s (PD) diseases. However, AAV limitations for delivering CRISPR modalities continue to impede viable therapeutic interventions targeting the brain. This review highlights challenges and strategies to deliver AAV-CRISPR-based therapeutic cargos for gene therapy applications in the CNS, with a particular focus on AD and PD preclinical studies. |
| format | Article |
| id | doaj-art-8ec3715449f846daba545f1cfda3e70b |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-8ec3715449f846daba545f1cfda3e70b2025-08-20T03:58:00ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-09-0136310263510.1016/j.omtn.2025.102635Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative diseaseBoris Kantor0Bernadette O'Donovan1Ornit Chiba-Falek2Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA; Viral Vector Core, Duke University School of Medicine, Durham, NC 27710, USA; Center for Advanced Genomic Technologies, Duke University School of Medicine, Durham, NC 27710, USA; Corresponding author: Boris Kantor, Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA.Division of Translational Brain Sciences, Department of Neurology, Duke University School of Medicine, Durham, NC 27710, USA; Center for Genomic and Computational Biology, Duke University School of Medicine, Durham, NC 27710, USADivision of Translational Brain Sciences, Department of Neurology, Duke University School of Medicine, Durham, NC 27710, USA; Center for Genomic and Computational Biology, Duke University School of Medicine, Durham, NC 27710, USA; Corresponding author: Ornit Chiba-Falek, Division of Translational Brain Sciences, Department of Neurology, Duke University School of Medicine, Durham, NC 27710, USA.Recent advances in gene-editing technologies offer new opportunities for drug development to treat unmet medical needs in central nervous system (CNS) disorders including neurogenerative diseases of the aging brain. The adeno-associated virus (AAV) is a promising and most widely utilized vector for gene therapy application including the CNS. AAV is characterized by high transduction efficiency in both dividing and non-dividing cells, low immunogenicity and toxicity, and exceptional tissue specificity. The development of clustered regularly interspaced short-palindromic repeat (CRISPR)-based technologies has revolutionized all aspects of modern sciences and created an innovative therapeutic toolkit with the potential to address a wide range of neurological diseases, including Alzheimer’s (AD) and Parkinson’s (PD) diseases. However, AAV limitations for delivering CRISPR modalities continue to impede viable therapeutic interventions targeting the brain. This review highlights challenges and strategies to deliver AAV-CRISPR-based therapeutic cargos for gene therapy applications in the CNS, with a particular focus on AD and PD preclinical studies.http://www.sciencedirect.com/science/article/pii/S2162253125001891MT: Delivery Strategiesadeno-associated vectorclustered regularly interspaced short-palindromic repeats/CRISPR-associated proteintranscriptional repressorgene editingepigenome-based editing |
| spellingShingle | Boris Kantor Bernadette O'Donovan Ornit Chiba-Falek Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease Molecular Therapy: Nucleic Acids MT: Delivery Strategies adeno-associated vector clustered regularly interspaced short-palindromic repeats/CRISPR-associated protein transcriptional repressor gene editing epigenome-based editing |
| title | Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease |
| title_full | Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease |
| title_fullStr | Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease |
| title_full_unstemmed | Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease |
| title_short | Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease |
| title_sort | trends and challenges of aav delivered gene editing therapeutics for cns disorders implications for neurodegenerative disease |
| topic | MT: Delivery Strategies adeno-associated vector clustered regularly interspaced short-palindromic repeats/CRISPR-associated protein transcriptional repressor gene editing epigenome-based editing |
| url | http://www.sciencedirect.com/science/article/pii/S2162253125001891 |
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