DNA and RNA base editors can correct the majority of pathogenic single nucleotide variants.
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
26 Feb 2024
26 Feb 2024
Historique:
received:
10
08
2023
accepted:
26
01
2024
medline:
27
2
2024
pubmed:
27
2
2024
entrez:
26
2
2024
Statut:
epublish
Résumé
The majority of human genetic diseases are caused by single nucleotide variants (SNVs) in the genome sequence. Excitingly, new genomic techniques known as base editing have opened efficient pathways to correct erroneous nucleotides. Due to reliance on deaminases, which have the capability to convert A to I(G) and C to U, the direct applicability of base editing might seem constrained in terms of the range of mutations that can be reverted. In this evaluation, we assess the potential of DNA and RNA base editing methods for treating human genetic diseases. Our findings indicate that 62% of pathogenic SNVs found within genes can be amended by base editing; 30% are G>A and T>C SNVs that can be corrected by DNA base editing, and most of them by RNA base editing as well, and 29% are C>T and A>G SNVs that can be corrected by DNA base editing directed to the complementary strand. For each, we also present several factors that affect applicability such as bystander and off-target occurrences. For cases where editing the mismatched nucleotide is not feasible, we introduce an approach that calculates the optimal substitution of the deleterious amino acid with a new amino acid, further expanding the scope of applicability. As personalized therapy is rapidly advancing, our demonstration that most SNVs can be treated by base editing is of high importance. The data provided will serve as a comprehensive resource for those seeking to design therapeutic base editors and study their potential in curing genetic diseases.
Identifiants
pubmed: 38409211
doi: 10.1038/s41525-024-00397-w
pii: 10.1038/s41525-024-00397-w
doi:
Types de publication
Journal Article
Langues
eng
Pagination
16Subventions
Organisme : Israel Science Foundation (ISF)
ID : 231/21
Organisme : Israel Science Foundation (ISF)
ID : 2039/20
Informations de copyright
© 2024. The Author(s).
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