| Literature DB >> 33623984 |
Suk See De Ravin1, Julie Brault1, Ronald J Meis2, Siyuan Liu3, Linhong Li4, Mara Pavel-Dinu5, Cicera R Lazzarotto6, Taylor Liu1, Sherry M Koontz1, Uimook Choi1, Colin L Sweeney1, Narda Theobald1, GaHyun Lee6, Aaron B Clark3, Sandra S Burkett7, Benjamin P Kleinstiver8,9, Matthew H Porteus5, Shengdar Tsai6, Douglas B Kuhns1, Gary A Dahl2, Stephen Headey10, Xiaolin Wu3, Harry L Malech1.
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.Entities:
Mesh：
Substances：
Year: 2021 PMID： 33623984 PMCID： PMC8120141 DOI： 10.1182/blood.2020008503
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113