CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by the death of motor neurons in the spinal cord and brain regions, leading to a reduced survival rate in patients. Nearly 20 gene mutations are associated with ALS, with SOD1, FUS, TARDBP, and C9orf72 mutation...

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Main Authors: Hamid Khan, Hammad Riaz, Adeel Ahmed, Mubin Mustafa Kiyani, Sahibzada Muhammad Jawad, Syed Shahab Ud Din Shah, Turki Abualait, Fawaz Al-hussain, Hong-Tao Li, Shahid Bashir
Format: Article
Language:English
Published: Elsevier 2025-12-01
Series:Regenerative Therapy
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352320425001634
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author Hamid Khan
Hammad Riaz
Adeel Ahmed
Mubin Mustafa Kiyani
Sahibzada Muhammad Jawad
Syed Shahab Ud Din Shah
Turki Abualait
Fawaz Al-hussain
Hong-Tao Li
Shahid Bashir
author_facet Hamid Khan
Hammad Riaz
Adeel Ahmed
Mubin Mustafa Kiyani
Sahibzada Muhammad Jawad
Syed Shahab Ud Din Shah
Turki Abualait
Fawaz Al-hussain
Hong-Tao Li
Shahid Bashir
author_sort Hamid Khan
collection DOAJ
description Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by the death of motor neurons in the spinal cord and brain regions, leading to a reduced survival rate in patients. Nearly 20 gene mutations are associated with ALS, with SOD1, FUS, TARDBP, and C9orf72 mutations being more common. Ninety percent of ALS cases are related to sporadic ALS, while the remaining 10 % are associated with familial ALS. CRISPR/Cas9, a genome engineering technology known as clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9, has the potential for gene editing and for studying the underlying mechanisms of ALS in mouse models. This technique enables neuroscientists to reverse mutations found in ALS mouse models, providing new hope for understanding the complexities of ALS. Additionally, this tool can create mutations to probe the functional changes of genetic diseases. Using CRISPR/Cas9 with an in vivo delivery method involving adeno-associated vectors, it is possible to silence mutations in the SOD1-linked ALS mouse model. Some limitations related to CRISPR/Cas9 have been discussed in previous studies and need to be addressed before clinical trials can proceed. In this review-based study, we summarise the latest research on CRISPR/Cas9 genome editing for ALS in mouse models and discuss its limitations and future prospects as well.
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spelling doaj-art-62ab19eab55d4a2faa4ddb6855a2edf82025-08-20T03:38:26ZengElsevierRegenerative Therapy2352-32042025-12-013057558310.1016/j.reth.2025.07.009CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse modelsHamid Khan0Hammad Riaz1Adeel Ahmed2Mubin Mustafa Kiyani3Sahibzada Muhammad Jawad4Syed Shahab Ud Din Shah5Turki Abualait6Fawaz Al-hussain7Hong-Tao Li8Shahid Bashir9Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Institute of Brain Science and Brain-inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, China; Shandong Institute of Brain Science and Brain-inspired Research, Jinan, 250117, China; Corresponding author. Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaMolecular Biology and Bio Interfaces Engineering Lab, Department of Biological Sciences, Faculty of Sciences, International Islamic University Islamabad. H10, Islamabad, 44000, PakistanInstitute of Brain Science and Brain-inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, ChinaShifa College of Medical Technology, Shifa Tameer-e-Millat University, Islamabad, PakistanDepartment of Zoology, Islamia College University, Peshawar, PakistanDepartment of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad Capital Territory, 15320, Islamabad, PakistanDepartment of Physical Therapy, College of Applied Medical Science, Imam Abdulrahman Bin Faisal University, Dammam, 32253, Saudi ArabiaDepartment Neurology, College of Medicine, King Saud University, P. O. Box 800, Riyadh, 11421, Kingdom of Saudi ArabiaDepartment of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Institute of Brain Science and Brain-inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, China; Shandong Institute of Brain Science and Brain-inspired Research, Jinan, 250117, ChinaNeuroscience Centre, King Fahad Specialist Hospital, Dammam, Saudi Arabia; King Salman Center for Disability Research, Riyadh, 11614, Saudi Arabia; Corresponding author. Neuroscience Center, King Fahad Specialist Hospital, Ammar Bin Thabit Street, Dammam, 31444, Saudi ArabiaAmyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by the death of motor neurons in the spinal cord and brain regions, leading to a reduced survival rate in patients. Nearly 20 gene mutations are associated with ALS, with SOD1, FUS, TARDBP, and C9orf72 mutations being more common. Ninety percent of ALS cases are related to sporadic ALS, while the remaining 10 % are associated with familial ALS. CRISPR/Cas9, a genome engineering technology known as clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9, has the potential for gene editing and for studying the underlying mechanisms of ALS in mouse models. This technique enables neuroscientists to reverse mutations found in ALS mouse models, providing new hope for understanding the complexities of ALS. Additionally, this tool can create mutations to probe the functional changes of genetic diseases. Using CRISPR/Cas9 with an in vivo delivery method involving adeno-associated vectors, it is possible to silence mutations in the SOD1-linked ALS mouse model. Some limitations related to CRISPR/Cas9 have been discussed in previous studies and need to be addressed before clinical trials can proceed. In this review-based study, we summarise the latest research on CRISPR/Cas9 genome editing for ALS in mouse models and discuss its limitations and future prospects as well.http://www.sciencedirect.com/science/article/pii/S2352320425001634Amyotrophic lateral sclerosis (ALS)CRISPR/Cas9Cas13Induced pluripotent cells (iPSCs)
spellingShingle Hamid Khan
Hammad Riaz
Adeel Ahmed
Mubin Mustafa Kiyani
Sahibzada Muhammad Jawad
Syed Shahab Ud Din Shah
Turki Abualait
Fawaz Al-hussain
Hong-Tao Li
Shahid Bashir
CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models
Regenerative Therapy
Amyotrophic lateral sclerosis (ALS)
CRISPR/Cas9
Cas13
Induced pluripotent cells (iPSCs)
title CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models
title_full CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models
title_fullStr CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models
title_full_unstemmed CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models
title_short CRISPR/Cas9 a genomic engineering technology for treatment in ALS mouse models
title_sort crispr cas9 a genomic engineering technology for treatment in als mouse models
topic Amyotrophic lateral sclerosis (ALS)
CRISPR/Cas9
Cas13
Induced pluripotent cells (iPSCs)
url http://www.sciencedirect.com/science/article/pii/S2352320425001634
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