ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Treatment of a Mouse Model of ALS by In Vivo Base Editing.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 3 of them syntheses that pooled it.
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Who cites it
153 citing papers in PubMed, 3 syntheses or guidelines pooled it, 242 citations in OpenAlex.
- Exploring Genetic Therapies Targeting Amyotrophic Lateral Sclerosis in Animal Models: A Systematic Review and Meta-Analysis.The journal of gene medicine · 2026Pooled it
- Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Pooled it
- Advances and Challenges in Gene Therapy for Neurodegenerative Diseases: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Base editing rescues a hereditary motor neuron disease in mouse and patient-derived iPSC organoid models.Molecular therapy. Advances · 2026Article
- Therapeutic frontiers in ALS: iPSC-based drug discovery, cell therapy, and gene therapy-Advances through 2026.Regenerative therapy · 2026Review
- Translating base editors: a decade of progress from the bench to the clinic.Nature reviews. Drug discovery · 2026Review
- Base editing for precision therapeutics.Cell genomics · 2026Review
- Integrative ALS therapy: gene targeted therapy by base editing and potential exercise rehabilitation as synergistic strategies for functional recovery.Physical activity and nutrition · 2026Article
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- In vivo CRISPR base editing for treatment of Huntington's disease.Nature biomedical engineering · 2026Article
- In vivo adenine base editing of mutant Galc gene ameliorates Krabbe disease progression.Genome medicine · 2026Article
- DNA and RNA editing for the therapy of human diseases: current status, challenges, and future prospects.Molecular biomedicine · 2026Review
- Application of extracellular vesicles in the CRISPR-based diagnosis and treatment: possibilities and challenges.Journal of biological engineering · 2026Review
- Gene Targeted Therapies for Neurodegenerative Disorders: Strategies and Implications in ALS and SMA.Genes · 2026Review
- Dual AAV vectors for efficient delivery of large transgenes.Nature protocols · 2026Review
- Advances in CRISPR Base Editing: From Molecular Evolution to Therapeutic Applications in Genomic Medicine.Journal of cellular and molecular medicine · 2026Review
- CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.Molecular therapy. Nucleic acids · 2026Review
- Coiled-coil heterodimer-mediated split base editing systems enable flexible and robust nucleotide substitutions.Nature communications · 2026Article
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Therapeutic in vivo genome editing: innovations and challenges in rAAV vector-based CRISPR delivery.Gene therapy · 2026Review
93 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal disorder that can be caused by mutations in the superoxide dismutase 1 (SOD1) gene. Although ALS is currently incurable, CRISPR base editors hold the potential to treat the disease through their ability to create nonsense mutations that can permanently disable the expression of the mutant SOD1 gene. However, the restrictive carrying capacity of adeno-associated virus (AAV) vectors has limited their therapeutic application. In this study, we establish an intein-mediated trans-splicing system that enables in vivo delivery of cytidine base editors (CBEs) consisting of the widely used Cas9 protein from Streptococcus pyogenes. We show that intrathecal injection of dual AAV particles encoding a split-intein CBE engineered to trans-splice and introduce a nonsense-coding substitution into a mutant SOD1 gene prolonged survival and markedly slowed the progression of disease in the G93A-SOD1 mouse model of ALS. Adult animals treated by this split-intein CRISPR base editor had a reduced rate of muscle atrophy, decreased muscle denervation, improved neuromuscular function, and up to 40% fewer SOD1 immunoreactive inclusions at end-stage mice compared to control mice. This work expands the capabilities of single-base editors and demonstrates their potential for gene therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.