Design and Engineering of Light-Induced Base Editors Facilitating Genome Editing with Enhanced Fidelity.
Adv Sci (Weinh)
; 11(5): e2305311, 2024 Feb.
Article
en En
| MEDLINE
| ID: mdl-38039441
ABSTRACT
Base editors, which enable targeted locus nucleotide conversion in genomic DNA without double-stranded breaks, have been engineered as powerful tools for biotechnological and clinical applications. However, the application of base editors is limited by their off-target effects. Continuously expressed deaminases used for gene editing may lead to unwanted base alterations at unpredictable genomic locations. In the present study, blue-light-activated base editors (BLBEs) are engineered based on the distinct photoswitches magnets that can switch from a monomer to dimerization state in response to blue light. By fusing the N- and C-termini of split DNA deaminases with photoswitches Magnets, efficient A-to-G and C-to-T base editing is achieved in response to blue light in prokaryotic and eukaryotic cells. Furthermore, the results showed that BLBEs can realize precise blue light-induced gene editing across broad genomic loci with low off-target activity at the DNA- and RNA-level. Collectively, these findings suggest that the optogenetic utilization of base editing and optical base editors may provide powerful tools to promote the development of optogenetic genome engineering.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN
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Edición Génica
Idioma:
En
Revista:
Adv Sci (Weinh)
Año:
2024
Tipo del documento:
Article
País de afiliación:
China