What is CRISPR?
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) are genes that quickly repeat DNA base sequences that are mechanically edited using a protein called Cas9. This system is based on the Cas9 protein’s ability to splice a given DNA sequence by being given a matching RNA code. This is incredibly similar to how alternative RNA splicing works in gene regulation for eukaryotic organisms. In the same way that alternative RNA splicing removes sequences of RNA code during the RNA processing stage of gene expression to create a variety of different proteins, the Cas9 protein removes sequences of code from DNA to synthesize unique proteins. When given a specific RNA sequence, the Cas9 protein will match that RNA sequence to a sequence of DNA, commencing the splicing of the DNA at that location. This process was discovered by Emmanuel Charpentier et al. in bacteria that use the Cas9 protein to target harmful DNA code inserted into the bacterial cytoplasm by viral organisms. Using the Cas9 protein, genetic engineers are able to remove DNA sequences in organisms to cause them to create different proteins and show a wanted phenotypic trait.
What is AAV?
AAV is a method of inserting DNA into a non-embryonic organism through structures similar to that of viruses. However, instead of containing harmful virus DNA, these vessels contain modified DNA using CRISPR to force a desired gene expression at a given location in the human body. AAV-based delivery systems are able to change a person’s genome during their lifetimes, potentially reducing the harm of/eliminating genetic diseases.
Experimentation
Dr. Peace Chinonyerem Ike et al. ran an experiment this year on pediatric males to test the effectiveness of using CRISPR editing through AAV to alter the genomes of certain cells. The diseases they chose are those that have been linked to the X-linked chromosome, meaning that men are more likely to get these diseases such as hemophilia and DMD. This is because X-linked traits in men come exclusively from the mother making it statistically more likely that they will express the phenotype of that gene. After experimentation over five years with treating patients, they saw that using CRISPR was significantly more effective than previous methods for reducing symptoms in these x-linked traits (such experiments include ZFNS).
What Does This Mean
After concluding that CRISPR can be used to treat genetic diseases on the X chromosome we may be able to expand its capabilities to more genetic illnesses such as Cystic Fibrosis that are autosomal. Using CRISPR, we can move medicine away from preventing side effects to outright curing illnesses at the level of the genome. This is a huge feat in the field of medicine and may predict a wave of new treatment strategies involving DNA modification in the future. I believe that, although this possible form of treatment is monumental, we must be incredibly cautious about using AAV-based systems as they may cause harmful mutations in the person’s genome. If we do not make sure that this treatment is safe we may cause multiple people to undergo harmful gene mutations and, for example, develop cancer. So you think that we will see the application of this treatment form in practice? If so, what do you think the ethical and moral ramifications are when using gene editing on a developed person?
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