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Utilizing Machine Learning with CRISPR-Cas9 to Combat Sickle Cell Anemia

Scientists from around the world are forming an invention that utilizes Machine Learning algorithms to identify where CRISPR-Cas9, a gene-editing technology, can best be applied without much trial and error. Clustered regularly interspaced short palindromic repeats, otherwise known as CRISPR, was modified from a naturally occurring genome editing system in bacteria that captures snippets of DNA from invading viruses and uses them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to identify the diseases. If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the virus’ DNA. The bacteria then use Cas9, the enzyme in the CRISPR mechanism, or a similar enzyme to cut the DNA apart at an area known as the protospacer adjacent motif, also known as PAMs, which disables the virus completely. Researchers and specialists use CRISPR to create a small piece of RNA with a short guide-like sequence that attaches to a specific target sequence of DNA in a genome. The RNA also binds to the Cas9 enzyme, and as in bacteria, the modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location. Once the DNA is cut, researchers use the cell's own DNA repair machinery or system to add or delete pieces of genetic material or can be utilized to make changes to the DNA by replacing an existing segment with a customized DNA sequence. However, a limitation to using CRISPR-Cas9 is that when modifying the genome, the technology is not always accurate and may possibly make mistakes while pinpointing where there is a deformity in the DNA. Moreover, the performance of CRISPR is profoundly dependent on trial and error and causes scientists and specialists to waste time and energy on ascertaining a resolution that can easily be found by altering the use of CRISPR and Machine Learning by combining them. Genome editing is of great interest in the prevention and treatment of human diseases. Currently, most research on genome editing is done to understand diseases using cells and animal models. Scientists are continuing to work to determine whether this approach is safe and effective for use in humans and it is being explored in research on a wide variety of diseases, including single-gene disorders such as cystic fibrosis, hemophilia, and sickle cell disease. It also holds promise for the treatment and prevention of more complex diseases, including cancer, heart disease, mental illness, and HIV.

CRISPR was first discovered in an E-coli bacteria in 1987 by a Japanese scientist named Yoshizumi Ishino and his team. They accidentally cloned a series of unusual repeated sequences strewed with spacer sequences while analyzing a gene responsible for the conversion of alkaline phosphatase. Ishino and his team were not aware of how these arrays functioned due to the lack of sufficient research on DNA sequences, leaving it a mystery that was yet to be solved at the time. Later on, in 1993, research done in the Netherlands by J.D van, Embden discovered that different strains in Mycobacterium tuberculosis, a pathogenic bacteria, had different spacer sequences. The various strains were classified based on a technique called spoligotyping which divided the strains into groups based on their spacer sequences. The sequences found were very similar to those present in other bacterial and archaeal genomes and were named CRISPRs by researchers Francisco Mojica and Rudd Jansen. When CRISPR was first discovered it was thought to be a DNA repair mechanism in thermophilic archaea and bacteria. In the 2000s, Mojica and his team noticed that the spacer sequences found in the bacteria and archaea were similar to those found in viruses, plasmids, and bacteriophages. They discovered that viruses cannot infect bacteria and archaea with these spacer sequences, suggesting that they served as an adaptive immune system in prokaryotes. This allowed a bacteria that contained such spacer sequences to attack viruses that may enter through their membranes by using the Cas9 protein to cleave the virus’s DNA sequence at complementary DNA and RNA sequences. The DNA cutting system in CRISPR was discovered by Kira S. Makarova, an Estonian -American scientist, and her team after conducting a comparative genome analysis of CRISPR and Cas genes. They concluded that CRISPR systems were very similar to another system known as RNA interference, in which proteins disable genes by severing their RNA sequences. The CRISPR gene-editing system attracted much attention in 2012 when scientists George Church, Jennifer Doudna, Emmanuelle Charpentier, and Feng Zheng utilized it as a mechanism to modify targeted regions of genomes. Since it had such great potential to dramatically transform the current stage of gene-editing, CRISPR was deemed Breakthrough of the Year in 2015. Overall, this invention focuses specifically on utilizing CRISPR with the assistance of machine learning to combat sickle cell anemia.

BY: Tauba Ashrafi

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