Adenine base editor engineering reduces editing of bystander cytosines.
Nat Biotechnol
; 39(11): 1426-1433, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34211162
ABSTRACT
Adenine base editors (ABEs) catalyze specific A-to-G conversions at genomic sites of interest. However, ABEs also induce cytosine deamination at the target site. To reduce the cytosine editing activity, we engineered a commonly used adenosine deaminase, TadA7.10, and found that ABE7.10 with a D108Q mutation in TadA7.10 exhibited tenfold reduced cytosine deamination activity. The D108Q mutation also reduces cytosine deamination activity in two recently developed high-activity versions of ABE, ABE8e and ABE8s, and is compatible with V106W, a mutation that reduces off-target RNA editing. ABE7.10 containing a P48R mutation displayed increased cytosine deamination activity and a substantially reduced adenine editing rate, yielding a TC-specific base editing tool for TC-to-TT or TC-to-TG conversions that broadens the utility of base editors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Citosina
/
Edição de Genes
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article