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Cited by 29Retinal Development and DisordersCRISPR and Genetic EngineeringVirus-based gene therapy research

Efficient correction of ABCA4 variants by CRISPR-Cas9 in hiPSCs derived from Stargardt disease patients

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Siles, Laura, Ruiz-Nogales, Sheila, Navinés-Ferrer, Arnau, Méndez-Vendrell, Pilar, Pomares, Esther·2023·Molecular Therapy - Nucleic Acids
DOI 10.1016/j.omtn.2023.02.032PMC PMC10034418
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Abstract

Inherited retinal dystrophies comprise a broad group of genetic eye diseases without effective treatment. Among them, Stargardt disease is the second most prevalent pathology. This pathology triggers progressive retinal degeneration and vision loss in children and adults. In recent years, the evolution of several genome editing technologies, such as the CRISPR-Cas9 system, has revolutionized disease modeling and personalized medicine. Human induced pluripotent stem cells also provide a valuable tool for in vitro disease studies and therapeutic applications. Here, we show precise correction of two ABCA4 pathogenic variants in human induced pluripotent stem cells from two unrelated patients affected with Stargardt disease. Gene editing was achieved with no detectable off-target genomic alterations, demonstrating efficient ABCA4 gene correction without deleterious effects. These results will contribute to the development of emerging gene and cell therapies for inherited retinal dystrophies.

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Cited by

Sorted by citations

Authors
Siles, L., Ruiz-Nogales, S., Navinés-Ferrer, A., Méndez-Vendrell, P., & Pomares, E.
Affiliations
Instituto de Microcirugía Ocular (ES)
Corresponding author
Pomares, Esther
ORCID
Pomares, Esther
Venue
Molecular Therapy - Nucleic Acids
Publisher
Elsevier BV
Published
2023-06
Volume
32
Pages
64-79
ISSN
2162-2531 (ISSN-L)
DOI
10.1016/j.omtn.2023.02.032
PMC
PMC10034418
OpenAlex
W4323044282
Cited by
29
References
4
Citations by year
2026: 9 · 2025: 9 · 2024: 7 · 2023: 4
FWCI
2.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Therapy — Nucleic Acids (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords
Stargardt disease, ABCA4, CRISPR/Cas9 genome editing, induced pluripotent stem cells, inherited retinal disease, retinal degeneration, off-target effects, gene therapy, cell therapy, disease modeling

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