As we already know, CRISPR-Cas editing tools are versatile and are promising as future gene-based therapies. Although many studies have shown CRISPR editing has a reasonable gene-editing efficiency, it has been suggested that CRISPR has a low gene editing efficiency for some systems such as stem cells, gametes, and immune cells. It has been hypothesised that small molecules could be used to improve the efficiency of CRISPR gene editing. Researchers would like to optimise CRISPR so that one-day CRISPR-based therapies become the new normal.
A group of researchers based at Dongguk University in Korea have released a publication in Cells, the researchers attempted to boost the efficiency of CRISPR gene editing by using epigenetic drugs. The researchers found that valproic acid boosted the gene-editing efficiency of CRISPR in embryonic stem cells and embryos. The knock-in efficiency was around 60% when using the CRISPR components alone. However, when using valproic acid in combination with the CRISPR components, the knock-in efficiency was around 100%. Valproic acid is a medication that is commonly used to treat a range of health conditions including bipolar disorder, epilepsy, and migraines.
The researchers believe that valproic acid was able to boost the gene-editing efficiency of CRISPR because valproic acid is an HDAC inhibitor, it causes epigenetic modifications by directly inhibiting histone deacetylases (HDAC). This causes the chromatin structure to relax, and subsequently, this allows the DNA to become more accessible to the CRISPR-Cas components for gene-editing. Therefore, the chromatin structure is an important factor that determines the gene-editing efficiency.