I learn in classes how genetic modification, specifically CRISPR-Cas9, is the future in the medical field. The problem that I have had with this idea is that there is little testing and low success rates when it comes to genetically modifying genes. CRISPR-Cas9 is a technology/protein that is able to cut out mutations, SNPs, or generally unwanted nucleotides and cut the DNA sequence. Causing it to repair itself and translate to something other than, for example, a tumor cell. This article has proved to me, that this technology is relevant today and is being used. In this article they use CRISPR to cut out the migration and invasion enhancer (MIEN1), which is an oncogene, that codes specifically for breast cancer. They used CRISPR to produce specific genomic deletions in the
MIEN1 gene which led to the silencing of its expression in breast
cancer cells. They claim that there were no off target effects and no deletion of any surrounding nucleotides. This is one of the first times I have heard of this protein effectively working without any off target effects or anything like that.
Van Treuren, T., & Vishwanatha, J. K. (2018). CRISPR deletion of MIEN1 in breast cancer cells. PLoS ONE, 13(10), 1–11. https://doi-org.dml.regis.edu/10.1371/journal.pone.0204976
In April 2015, a Chinese research team published the first use of CRISPR Cas-9 in human embryos engineering the mutation of β-thalassemia, which would alter the human embryos germ-line. These embryos were not implanted anywhere but if they were: Do you believe that this is ethical to alter the germ-line therefore altering the future generations that would come from this embryo? Do you think that this upholds the value of autonomy for those future generations?
ReplyDeleteNewson & Wrigley 2016 Being human. Austral. Quart. 87:3-8.
An article reports the development of precision genome-engineering tools based on the RNA-guided Cas9 nuclease from type II prokaryotic clustered regularly interspaced short palindromic repeats adaptive immune system. The researchers aimed to connect the prokaryotic RNA-programmable nuclease system to introduce target double-stranded breaks in mammalian chromosomes through heterogeneous expression of key components. They tested if heterogeneous expression of the CRISPR system can achieve targeted cleavage of mammalian chromosomes. The results demonstrate a minimal three-component system for efficient RNA-guided genome modification in mammalian cells. The researchers also explored the generalizability of RNA-guided genome editing in eukaryotic cells. They tested targeting of additional genomic loci in both human and mouse cells. The results demonstrate the utility of CRISPR for facilitating targeted genomic insertions. The S. pyogenes CRISPR system can be heterologously reconstituted in mammalian cells to facilitate efficient genome editing.
ReplyDeleteI would argue that these major advancements in genome editing could tremendously assist people in living more efficient lives, but it still remains unethical with so much uncertainty of any consequences.
Cong, L., et al. “Multiplex Genome Engineering Using CRISPR/Cas Systems.” Science, vol. 339, no. 6121, 2013, pp. 819–823., doi:10.1126/science.1231143.
Interesting post, I am actually writing my Master's thesis on CRISPR. Yes, it is true that CRISPR has some problems and there is still a lot we don't know about it yet, but it is being used for a lot of great things already especially in a research setting. In research settings, CRISPR has been used to successfully alter the DNA of mosquitos, mice, pigs, and even human embryos (Gantz et al., 2015; Zhao et al., 2017; Ma et al., 2017). In mosquito populations, researchers have used CRISPR to induce a gene drive that has the ability to work in the germ-line of these mosquitos to induce infertility or expression of malaria resistant genes (Gantz et al., 2015). They are actually researching altering DNA of pig zygotes to knock out genes involved in rejection of xenotransplantation (Petersen et al., 2016). There are lots of other great uses of CRISPR that I won't go into detail with because it would take up pages of writing, but if you're interestested let me know and we can talk about it! You are right though, it does have the potential to produce off target effects; however, there are things we can do do to improve its efficacy (Fu et al., 2013). It can also produce an immune response in humans due to an adaptive immune response, so that is also a potential problem (Charlesworth et al., 2018). . However, since it is an adaptive immunity this may not be a problem for embryos (Charlesworth et al., 2018).
ReplyDeleteCharlesworth, C. T., Deshpande, P. S., Dever, D. P., Dejene, B., Gomez-Ospina, N., Mantri, S., … Porteus, M. H. (2018). Identification of Pre-Existing Adaptive Immunity to Cas9 Proteins in Humans. BioRxiv, 243345. https://doi.org/10.1101/243345
Fu, Y., Foden, J. A., Khayter, C., Maeder, M. L., Reyon, D., Joung, J. K., & Sander, J. D. (2013). High frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nature Biotechnology, 31(9), 822–826. https://doi.org/10.1038/nbt.2623
Gantz, V. M., Jasinskiene, N., Tatarenkova, O., Fazekas, A., Macias, V. M., Bier, E., & James, A. A. (2015). Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proceedings Of The National Academy Of Sciences Of The United States Of America, 112(49), E6736–E6743. https://doi.org/10.1073/pnas.1521077112
Ma, H., Marti-Gutierrez, N., Park, S.-W., Wu, J., Lee, Y., Suzuki, K., … Mitalipov, S. (2017). Correction of a pathogenic gene mutation in human embryos. Nature, 548(7668), 413–419. https://doi.org/10.1038/nature23305
Petersen, B., Frenzel, A., Lucas-Hahn, A., Herrmann, D., Hassel, P., Klein, S., … Niemann, H. (2016). Efficient production of biallelic GGTA1 knockout pigs by cytoplasmic microinjection of CRISPR/Cas9 into zygotes. Xenotransplantation, 23(5), 338–346. https://doi.org/10.1111/xen.12258
Zhao, J., Zhao, J., Xu, G., Wang, Z., Gao, J., Cui, S., & Liu, J. (2017). Deletion of Spata2 by CRISPR/Cas9n causes increased inhibin alpha expression and attenuated fertility in male mice. Biology of Reproduction, 97(3), 497–513. https://doi.org/10.1093/biolre/iox093