Compact zinc finger architecture utilizing toxin-derived cytidine deaminases for highly efficient base editing in human cells.
Nat Commun
; 15(1): 1181, 2024 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-38360922
ABSTRACT
Nucleobase editors represent an emerging technology that enables precise single-base edits to the genomes of eukaryotic cells. Most nucleobase editors use deaminase domains that act upon single-stranded DNA and require RNA-guided proteins such as Cas9 to unwind the DNA prior to editing. However, the most recent class of base editors utilizes a deaminase domain, DddAtox, that can act upon double-stranded DNA. Here, we target DddAtox fragments and a FokI-based nickase to the human CIITA gene by fusing these domains to arrays of engineered zinc fingers (ZFs). We also identify a broad variety of Toxin-Derived Deaminases (TDDs) orthologous to DddAtox that allow us to fine-tune properties such as targeting density and specificity. TDD-derived ZF base editors enable up to 73% base editing in T cells with good cell viability and favorable specificity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Citidina Desaminase
/
Edição de Genes
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article