CRISPR/Cas9: The Future of Medicine
Crawford, Mark. “8 Ways CRISPR/Cas9 Can Change the World.” Digital Image. American Society of Mechanical Engineers (ASME). Accessed December 28, 2017. https://www.asme.org/engineering-topics/articles/bioengineering/8-ways-crisprcas9-can-change-world.
Scientists have discovered a revolutionary gene-editing technology with the hope of fighting diseases. The technology is known as CRISPR/Cas9. CRISPR is an acronym that stands for Clustered Regularly Interspaced Short Palindromic Repeats. CRISPRs are chunks of DNA originally found in bacteria that repeat themselves. In between CRISPRs are varied spaces of DNA called spacers that encode for fighting off previous invading viruses and serve as a genetic memory. In a way, CRISPRs and spacers act as an immune system for bacteria. CRISPR RNA combines with the Cas9 protein to function as a detection system for foreign DNA, which is then destroyed by the RNA guided interference. While originating as a defense mechanism for bacteria to fight off viruses, the CRISPR/Cas9 system is now being manipulated by researchers to be used as molecular scissors. CRISPR/Cas9 technology is being engineered to cut defective genes in human DNA and repair them by deleting the mutated genes or by replacing them with healthy ones. Figure 1
Figure 1: Draper, Don. “CRISPR-Cas9 Human DNA Modification.” Digital Image. Imgur. Accessed December 28, 2017. https://imgur.com/gallery/FseAU
CRISPR/Cas9 has been put to the test by scientists in Dr. Corn’s Laboratory at University of California Berkeley. The team has used CRISPR/Cas9 to develop a possible cure for Sickle Cell Anemia. Sickle Cell Anemia (SCA) is an autosomal recessive genetic disease in which red blood cells become sickle-shaped. It is caused by a single-base substitution in the β-globin (HBB) gene, which is located on chromosome 11. As a result, valine is produced instead of glutamic acid, causing the production of sickle haemoglobin (HbS). This causes red blood cells to become distorted into a sickle shape, leading to the blockage of blood vessels. Due to the lack of blood flow, severe pain, infections, and organ failure occur. The median life span of patients with SCA is 42 years for females and 38 for males. The only current treatments available for patients suffering from SCA include blood transfusions, drug therapy such as hydroxyurea, or bone marrow transplants. All of these treatments have the potential for harmful side effects, and none of them have increased the average lifespan of people with SCA beyond middle age. Scientists are hoping CRISPR/Cas9 will solve these problems and give people with SCA a fighting chance at a prolonged better quality of life.
In order to treat SCA with CRISPR/Cas9, hematopoietic stem and progenitor cells (HSPCs) found in the bone marrow and peripheral blood are targeted for editing because they have the potential to differentiate into healthy red blood cells. The Cas9 protein combined with a specifically engineered guide RNA is inserted into the HSPC cells and directed by the RNA guide to attach at the 6th codon on chromosome 11 and cut the defective DNA with the thymine nucleotide. A corrected healthy DNA sequence with an adenine nucleotide is simultaneously inserted, correcting the mutation. Cutting the thymine out and replacing it with adenine at this point in the DNA produces glutamic acid instead of valine resulting in normal haemoglobin with round red blood cells. The blood flows freely through the circulatory system relieving patients of their pain and preventing infections and organ failure.
Although experimentation in Dr. Corn’s lab is conducted primarily in mice, human clinical trials using CRISPR/Cas9 are currently being conducted by Doctor Lu You of Sichuan University in China to treat patients with Lung Cancer. [5} The cutting edge CRISPR/Cas9 technology is not yet approved for patient care today, but its debut in the medical world as a common treatment could be just around the corner.
 Mojica, Francisco J.M., & Montoliu, Lluis. “On the Origin of CRISPR-Cas Technology: From Prokaryotes to Mammals.” CellPress 24, no.10 (2016). https://www.ncbi.nlm.nih.gov/pubmed/27401123.
 DeWitt, Mark A., Magis, Wendy, Bray, Nicholas L., Wang, Tianjiao, Berman, J., Urbinati, Fabrizi., Heo, Seok-Jin., Mitros, Therese., Muñoz, Denise P., Boffelli, Dario., Kohn, Donald B., Walters, Mark C., Carroll, Dana., Martin, David I.K., and Corn, Jacob E. “Selection-Free Genome Editing .” Science Translational Medicine 8, no. 360 (2017). http://stm.sciencemag.org/content/8/360/360ra134.
 Tasan, Ipek, Jain, Surbhi, and Zhao, Huimin. “Use of Genome-Editing Tools to Treat Sickle Cell Disease.” Human Genetics 135, no. 9 (2016). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002234/.
 DeWitt et al. “Selection-Free Genome Editing.” Science Translational Medicine 8, no.360 (2017). http://stm.sciencemag.org/content/8/360/360ra134.
 Cyranoski, David. “Chinese scientists to pioneer first human CRISPR trial.” Nature (2016). http://www.nature.com/news/chinese-scientists-to-pioneer-first-human-crispr-trial-1.20302.