Enhanced homology-directed repair for highly efficient gene editing in hematopoietic stem/progenitor cells.
Blood
; 137(19): 2598-2608, 2021 05 13.
Article
em En
| MEDLINE
| ID: mdl-33623984
ABSTRACT
Lentivector gene therapy for X-linked chronic granulomatous disease (X-CGD) has proven to be a viable approach, but random vector integration and subnormal protein production from exogenous promoters in transduced cells remain concerning for long-term safety and efficacy. A previous genome editing-based approach using Streptococcus pyogenes Cas9 mRNA and an oligodeoxynucleotide donor to repair genetic mutations showed the capability to restore physiological protein expression but lacked sufficient efficiency in quiescent CD34+ hematopoietic cells for clinical translation. Here, we report that transient inhibition of p53-binding protein 1 (53BP1) significantly increased (2.3-fold) long-term homology-directed repair to achieve highly efficient (80% gp91phox+ cells compared with healthy donor control subjects) long-term correction of X-CGD CD34+ cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Transplante de Células-Tronco Hematopoéticas
/
Reparo do DNA
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Proteína 1 de Ligação à Proteína Supressora de Tumor p53
/
Edição de Genes
/
NADPH Oxidase 2
/
Doença Granulomatosa Crônica
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Blood
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Moldávia