The Future of Gene Editing

CRISPR is a technique in which the genome is edited after the creation of a double stranded break to a target DNA sequence (Ran et al, 2013). Once the break has been created, CRISPR is introduced with CAS9 in order to repair the break in one of two ways. Homology directed repair (HDR) is the process of using a template strand of DNA creating a precise correction of the double stranded break. Nonhomologous end joining (NHEJ) is the process of repair that does not utilize a template strand and oftentimes leads to more mutations. 

Somatic gene editing in which the cells of an adult are targeted is the most common form of CRISPR. As this technology continues to grow, so do the clinical applications. For example, CRISP has been linked to the treatment of diseases including cancer, muscular dystrophy, cystic fibrosis, and Huntington’s disease. In terms of cancer, currently there are clinical trials utilizing CAR-T cells. These trials are being completed in china and focus on targeting two types of malignancies; B cell leukemia and lymphoma. CAR-T is chimeric antigen receptor (CAR)- engineered T cells and in these trials CD19 is the targeted antigen (Liu, Song & Liu, 2017). CAR-T cells can cross the blood-brain barrier and they mount an immune attack against cancerous cells by connecting to a specific antigen that is located on the surface of the mutated cells. 

Germline editing utilizing CRISPR is still banned in most countries and embryos can not be implanted once they have had their genome edited. Given this fact, do you think that germline editing should be allowed in embryos? Should these embryos be implanted? Keep in mind this has been accomplished by a Chinese scientist in 2018 as an attempt to knock out a gene that is associated with HIV. While he successfully edited the genomes of these ‘CRISPR babies’, the unknown long term and off target effects could be detrimental as these children develop. 

If you wish to learn more about CAR-T cell therapies, here is a link with an article and video describing the process. https://blog.dana-farber.org/insight/2017/06/car-t-cell-therapy/

 

References:

Liu, B., Song, Y., & Liu, D. (2017). Clinical trials of CAR-T cells in China. Journal of hematology & oncology, 10(1), 166.

Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013). Genome engineering using the CRISPR-Cas9 system. Nature protocols, 8(11), 2281.