AI Article Synopsis
- * A previous approach using Cas9 mRNA and an oligodeoxynucleotide donor had the potential to repair genetic mutations but wasn't efficient enough in inactive CD34+ hematopoietic cells for use in patients.
- * This study found that temporarily blocking the protein 53BP1 boosted the efficiency of gene repair by 2.3 times, resulting in a successful correction in 80% of X-CGD CD34+ cells, offering a promising pathway for clinical treatment.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120141 | PMC |
| http://dx.doi.org/10.1182/blood.2020008503 | DOI Listing |
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