Publication Date
9-1-2023
Document Type
Article
Publication Title
Biochemistry and Biophysics Reports
Volume
35
DOI
10.1016/j.bbrep.2023.101513
Abstract
The CRISPR/Cas9 technology is a prominent genome-editing tool capable of producing a double-strand break in the genome. However, the modification of hematopoietic stem cells via the homology-directed repair pathway is still inefficient. Therefore, we hypothesize that histone deacetylase inhibitors, such as valproic acid (VPA) and sodium butyrate (NaB), could enhance HDR efficiency by increasing the accessibility of the genome-editing machinery. To address the potential utilization of HDAC inhibitors therapeutically, we began by assessing the effect of VPA and NaB on two cell lines representative of the two hematopoietic stem cell lineages. No statistically significant effect on cell growth or viability was observed at concentrations as high as 5 mM. At a concentration as low as 0.005 mM NaB, an enhancement in CRISPR cutting efficiency was evidenced in both cell lines. This enhancement did not appear to be locus-specific. However, an enhancement in cutting efficiency following VPA treatment does appear to be. HDR efficiency was enhanced greater than two-fold with the use of 0.005 mM VPA. These results are promising and suggest the consideration of treatment with an HDAC inhibitor in CRISPR/Cas9 genome editing protocols.
Funding Number
4T34GM008253
Funding Sponsor
National Institute of General Medical Sciences
Keywords
CRISPR, Gene editing, Histone deacetylase inhibitors, Sodium butyrate, Valproic acid
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Department
Biological Sciences
Recommended Citation
Ymer Björnson, Codey Y. Huang, Jaedyn L. Rollins, Guadalupe Castañeda, Navneet Kaur, Emiko Yamamoto, and Jennifer M. Johnston. "The effect of histone deacetylase inhibitors on the efficiency of the CRISPR/Cas9 system" Biochemistry and Biophysics Reports (2023). https://doi.org/10.1016/j.bbrep.2023.101513
