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:

  1. 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
  2. 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.
  3. 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
  4. 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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