By Tamar Nicole Soussana, Staff Writer
This year, the Nobel Prize in chemistry was awarded to two female scientists, Emmanuelle Charpentier and Jennifer A. Doudna, for their work on developing a method for genome editing, known as CRISPR-Cas9. In short, this technology can edit the genome, or the genetic material of an organism, which is made up of DNA. Not only does their discovery impact the world of biotechnology and offer future therapeutic solutions to genetic diseases, it also inspires more women to enter the field of science. From 1901 to 2020, the Nobel Prize in chemistry was awarded to 185 scientists, of which 7 were women. The fact that two women were awarded the Nobel Prize this year is inspiring to me as an aspiring scientist, as well as to countless other women worldwide.
Like all scientific work, no discovery is made without plenty of previous research. Many individual findings eventually led to CRISPR-Cas9. DNA is made up of nucleotides, each having a specific partner or nucleotide pair. This contributes to the base pairing, or complementary elements, of DNA. In 1987, scientists reported repeating base pair sequences, or blocks of DNA with the same nucleotide pairs, in the DNA of Escherichia coli. It was eventually found that these repeats were common in prokaryotes, and were coined CRISPR, or clustered regularly interspaced short palindromic repeats. While they shared the base pair repeats, the spacers in-between were variable. Another important finding was Cas, or CRISPR associated genes, which are a group of genes that are always located near CRISPRs.
In 2005, it was discovered that the CRISPR genes of prokaryotes contributed to their immunity towards viruses because the CRISPR spacers matched the viral DNA. It was hypothesized that after a bacterium survived viral infection, it added a part of the virus’s genetic code into its genome as a type of memory for the next infection. It was later proven that the RNA transcription of CRISPR (crRNA) binds to Cas proteins in a complex that can target foreign DNA and cleave, or cut it. Therefore the identical spacers as well as the Cas proteins are important in viral immunity for prokaryotes.
In 2011, Emanuelle Charpentier and her colleagues discovered an RNA species near the CRISPR locus named tracrRNA, which has complementary base pairing to the repeated regions of CRISPR. After further experiments, Charpentier found that the Cas9 protein and tracrRNA are vital for the processing and maturation of crRNA, forming a complex which leads to the cleavage of viral DNA.
In a collaboration with Jennifer A. Doudna in 2012, the two scientists discovered that tracrRNA not only triggers the processing of crRNA, but activates the crRNA guided DNA cleavage with Cas9. Charpentier and Doudna also performed a very important experiment in which they fused the RNA components into an active, single guide RNA molecule (sgRNA). Furthermore, they demonstrated that the sgRNA could be modified to target specific DNA sequences and result in the cleavage of particular sections of a DNA molecule.
In summation, Charpentier and Doudna created a two-component system, involving sgRNA and Cas9, which can be configured to cleave DNA sequences and could be used for programmable genome editing. This technology allows researchers a multitude of possibilities, one of which is to isolate mutations associated with diseases and test it for treatment. Currently, this technology is being used to develop a treatment for sickle cell disease, a disease in which a defective form of hemoglobin is produced and red blood cells sickle, unable to properly transport oxygen.
In treatment of sickle cell disease, scientists extract cells from the patient’s bone marrow, and use CRISPR-Cas9 to edit a gene to code for the production of fetal hemoglobin, which as of now has proven to compensate for the sickled red blood cells in the patient’s body.
While CRISPR technology can be used for good, it also has the potential for use in ethically questionable situations. As an example, a Chinese scientist used CRISPR-Cas9 technology to genetically modify embryos in order to protect them from developing HIV. As it turns out, this scientist may not have followed strict ethical guidelines or regulations. Doudna herself denounced this scientist’s use of the technology she helped discover, and said that gene-editing of human embryos should only be used when there is no viable alternative approach.
While there may have to be regulations in place for the CRISPR-Cas9 technology, it has great potential to treat so many patients worldwide. Virtually all genetic diseases have a possibility of treatment with this amazing discovery as it provides the ability to edit any genome. I hope that this year’s Nobel Prize in chemistry winners not only inspire the health of millions, but inspire other women to know that they can accomplish great things in the world of science.
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Sources:
https://www.nobelprize.org/uploads/2020/10/popular-chemistryprize2020.pdf
https://www.nobelprize.org/uploads/2020/10/advanced-chemistryprize2020.pdf