ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
In vivo adenine base editing rescues adrenoleukodystrophy in a humanized mouse model.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Review
- Prime editing in neuropsychiatric disorders: From mutation-specific target selection to clinical translation.Neuroprotection (Chichester, England) · 2026Review
- In vivo adenine base editing of mutant Galc gene ameliorates Krabbe disease progression.Genome medicine · 2026Article
- In vivo base editing rescues ADPKD in a humanized mouse model.Nature communications · 2025Article
- Research progress of base editing and prime editing tools based on the CRISPR/Cas system.Molecular therapy. Nucleic acids · 2025Review
- Review
- From gene to therapy: a review of deciphering the role of ABCD1 in combating X-Linked adrenoleukodystrophy.Lipids in health and disease · 2024Review
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
X-linked adrenoleukodystrophy (ALD), an inherited neurometabolic disorder caused by mutations in ABCD1, which encodes the peroxisomal ABC transporter, mainly affects the brain, spinal cord, adrenal glands, and testes. In ALD patients, very-long-chain fatty acids (VLCFAs) fail to enter the peroxisome and undergo subsequent β-oxidation, resulting in their accumulation in the body. It has not been tested whether in vivo base editing or prime editing can be harnessed to ameliorate ALD. We developed a humanized mouse model of ALD by inserting a human cDNA containing the pathogenic variant into the mouse Abcd1 locus. The humanized ALD model showed increased levels of VLCFAs. To correct the mutation, we tested both base editing and prime editing and found that base editing using ABE8e(V106W) could correct the mutation in patient-derived fibroblasts at an efficiency of 7.4%. Adeno-associated virus (AAV)-mediated systemic delivery of NG-ABE8e(V106W) enabled robust correction of the pathogenic variant in the mouse brain (correction efficiency: ∼5.5%), spinal cord (∼5.1%), and adrenal gland (∼2%), leading to a significant reduction in the plasma levels of C26:0/C22:0. This established humanized mouse model and the successful correction of the pathogenic variant using a base editor serve as a significant step toward treating human ALD disease.
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