CRISPR-Pass

Gene Rescue of Nonsense Mutations Using Adenine Base Editors

Choongil Lee, Dong Hyun Jo, Gue Ho Hwang, Jihyeon Yu, Jin Hyoung Kim, Se eun Park, Jin Soo Kim, Jeong Hun Kim, Sangsu Bae

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

A nonsense mutation is a substitutive mutation in a DNA sequence that causes a premature termination during translation and produces stalled proteins, resulting in dysfunction of a gene. Although it usually induces severe genetic disorders, there are no definite methods for inducing read through of premature termination codons (PTCs). Here, we present a targeted tool for bypassing PTCs, named CRISPR-pass, that uses CRISPR-mediated adenine base editors. CRISPR-pass, which should be applicable to 95.5% of clinically significant nonsense mutations in the ClinVar database, rescues protein synthesis in patient-derived fibroblasts, suggesting potential clinical utility. Lee et al. showed that CRISPR-pass, based on adenine base editors, would be a targeted tool for bypassing premature termination codons. This system could be applicable to ∼95% of clinically significant nonsense mutations, related to genetic diseases, in the ClinVar database.

Original languageEnglish
Pages (from-to)1364-1371
Number of pages8
JournalMolecular Therapy
Volume27
Issue number8
DOIs
StatePublished - 7 Aug 2019

Fingerprint

Clustered Regularly Interspaced Short Palindromic Repeats
Nonsense Codon
Adenine
Genes
Inborn Genetic Diseases
Protein Databases
Fibroblasts
Databases
Mutation

Keywords

  • CRISPR-Cas9
  • base editing
  • nonsense mutation
  • premature termination codon
  • stop codon read through

Cite this

Lee, C., Hyun Jo, D., Hwang, G. H., Yu, J., Kim, J. H., Park, S. E., ... Bae, S. (2019). CRISPR-Pass: Gene Rescue of Nonsense Mutations Using Adenine Base Editors. Molecular Therapy, 27(8), 1364-1371. https://doi.org/10.1016/j.ymthe.2019.05.013
Lee, Choongil ; Hyun Jo, Dong ; Hwang, Gue Ho ; Yu, Jihyeon ; Kim, Jin Hyoung ; Park, Se eun ; Kim, Jin Soo ; Kim, Jeong Hun ; Bae, Sangsu. / CRISPR-Pass : Gene Rescue of Nonsense Mutations Using Adenine Base Editors. In: Molecular Therapy. 2019 ; Vol. 27, No. 8. pp. 1364-1371.
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abstract = "A nonsense mutation is a substitutive mutation in a DNA sequence that causes a premature termination during translation and produces stalled proteins, resulting in dysfunction of a gene. Although it usually induces severe genetic disorders, there are no definite methods for inducing read through of premature termination codons (PTCs). Here, we present a targeted tool for bypassing PTCs, named CRISPR-pass, that uses CRISPR-mediated adenine base editors. CRISPR-pass, which should be applicable to 95.5{\%} of clinically significant nonsense mutations in the ClinVar database, rescues protein synthesis in patient-derived fibroblasts, suggesting potential clinical utility. Lee et al. showed that CRISPR-pass, based on adenine base editors, would be a targeted tool for bypassing premature termination codons. This system could be applicable to ∼95{\%} of clinically significant nonsense mutations, related to genetic diseases, in the ClinVar database.",
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Lee, C, Hyun Jo, D, Hwang, GH, Yu, J, Kim, JH, Park, SE, Kim, JS, Kim, JH & Bae, S 2019, 'CRISPR-Pass: Gene Rescue of Nonsense Mutations Using Adenine Base Editors', Molecular Therapy, vol. 27, no. 8, pp. 1364-1371. https://doi.org/10.1016/j.ymthe.2019.05.013

CRISPR-Pass : Gene Rescue of Nonsense Mutations Using Adenine Base Editors. / Lee, Choongil; Hyun Jo, Dong; Hwang, Gue Ho; Yu, Jihyeon; Kim, Jin Hyoung; Park, Se eun; Kim, Jin Soo; Kim, Jeong Hun; Bae, Sangsu.

In: Molecular Therapy, Vol. 27, No. 8, 07.08.2019, p. 1364-1371.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Kim, Jin Hyoung

AU - Park, Se eun

AU - Kim, Jin Soo

AU - Kim, Jeong Hun

AU - Bae, Sangsu

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AB - A nonsense mutation is a substitutive mutation in a DNA sequence that causes a premature termination during translation and produces stalled proteins, resulting in dysfunction of a gene. Although it usually induces severe genetic disorders, there are no definite methods for inducing read through of premature termination codons (PTCs). Here, we present a targeted tool for bypassing PTCs, named CRISPR-pass, that uses CRISPR-mediated adenine base editors. CRISPR-pass, which should be applicable to 95.5% of clinically significant nonsense mutations in the ClinVar database, rescues protein synthesis in patient-derived fibroblasts, suggesting potential clinical utility. Lee et al. showed that CRISPR-pass, based on adenine base editors, would be a targeted tool for bypassing premature termination codons. This system could be applicable to ∼95% of clinically significant nonsense mutations, related to genetic diseases, in the ClinVar database.

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Lee C, Hyun Jo D, Hwang GH, Yu J, Kim JH, Park SE et al. CRISPR-Pass: Gene Rescue of Nonsense Mutations Using Adenine Base Editors. Molecular Therapy. 2019 Aug 7;27(8):1364-1371. https://doi.org/10.1016/j.ymthe.2019.05.013