Brefeldin A (BFA)
Biological Activity
Brefeldin A (BFA) is a fungal lactone metabolite that (reversibly) inhibits intracellular protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus. [1] It also activates the sphinogomyelin cycle, [2] and exhibits considerable in vitro and in vivo antitumor activity, associated with autophagy and apoptosis. [3] It was also found to increase CRISPR-mediated HDR efficiency, but more research is needed to understand its underlying mechanism.
Successful Applications in CRISPR
(i) Brefeldin A enhanced CRISPR-mediated HDR efficiency in mouse E14 embryonic stem cells (ESCs) by 2-fold for large fragment insertions (via a circular template plasmid). Maximal effects were achieved with 0.1 μM of Brefeldin A. [4]
Reference:
- Ktistakis, N., Linden, M. & Roth, M. Action of brefeldin A blocked by activation of a pertussis-toxin-sensitive G protein. Nature 356, 344–346 (1992). https://doi.org/10.1038/356344a0
- Linardic, C. M., Jayadev, S., & Hannun, Y. A. (1996). Activation of the sphingomyelin cycle by brefeldin A: effects of brefeldin A on differentiation and implications for a role for ceramide in regulation of protein trafficking. Cell growth & differentiation: the molecular biology journal of the American Association for Cancer Research, 7(6), 765–774.
- Zhou, L., Gao, W., Wang, K., Huang, Z., Zhang, L., Zhang, Z., Zhou, J., Nice, E. C., & Huang, C. (2019). Brefeldin A inhibits colorectal cancer growth by triggering Bip/Akt-regulated autophagy. FASEB journal: official publication of the Federation of American Societies for Experimental Biology, 33(4), 5520–5534. https://doi.org/10.1096/fj.201801983R
- Yu, C., Liu, Y., Ma, T., Liu, K., Xu, S., Zhang, Y., Liu, H., La Russa, M., Xie, M., Ding, S., & Qi, L. S. (2015). Small molecules enhance CRISPR genome editing in pluripotent stem cells. Cell stem cell, 16(2), 142–147. https://doi.org/10.1016/j.stem.2015.01.003
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