By Sierrah Laurent, Research Team Member
The discipline of science performs several tasks for the benefit of our society, including the generation of new information, the enhancement of education, and the improvement of our quality of life. You may have heard of CRISPR-Cas 9 genome editing, but have you considered the minds behind this revolutionary tool?
While numerous researchers have contributed to our understanding of CRISPR-Cas 9 genome editing, Jennifer Dounda was one of the pioneers in shaping this technology into what it is today.
When Dr. Dounda moved to Hilo, Hawaii at the age of 7, her mother was a history professor at a community college, and her father was a professor of literature at the University of Hawaii. Since most of her peers were of Polynesian and Asian descent, she frequently felt alienated as a young girl since her appearance differed. Her isolation led her to develop a certain bookishness that prompted her to focus on the chemistry of biological systems. However, little did she know that she would eventually become a professor of Molecular and Cell Biology at UC Berkeley and a primary investigator at the Howard Hughes Medical Institute.
CRISPR-Cas 9 genome editing? Never heard of it!
Originally, prokaryotes—bacteria and archaea—used CRISPR-Cas 9 as a microbial "immune system" to guard against phage infection. However, thanks to Dr. Dounda and her research partner Emmanuelle Charpentier's work, by isolating and slightly altering components of the prokaryote's defence mechanism, CRISPR-Cas 9 became a special genome editing tool that enables geneticists and medical researchers to delete, insert, or change DNA sequences in specific regions of the genome
The Cas enzyme (blue) and guide RNA (RNA-targeting device, purple) make up CRISPR. The DNA is cut by Cas when the guide RNA and the target DNA (orange) align. The DNA can then have a new segment (green) inserted to it.
Credit: National Institute of General Medical Sciences, National Institutes of Health
Two essential components make up the system and modify the DNA strands. These are:
An enzyme called Cas9. This functions as a set of "molecular scissors" that can cut the two DNA strands at a precise point in the CRISPR. The DNA is cut by Cas when the guide RNA and the target DNA (orange) align. The DNA can then have a new segment (green) inserted to it.
An RNA called guide RNA (gRNA). A brief segment of pre-designed RNA sequence (approximately 20 bases long) enclosed in a larger RNA scaffold makes up gRNA. The pre-designed sequence 'guides' Cas9 to the appropriate region of the genome while the scaffold component binds to DNA. This guarantees that the Cas9 enzyme performs a cut at the appropriate location in the DNA.
It’s important to note that as the guide RNA is designed to find and bind to a specific sequence in the DNA, it has RNA bases that are complementary to a target DNA sequence in the genome.
Future Implications and Patent Dispute
The development of the Crispr-Cas9 tool is an example of how seemingly obscure basic biology research ended up having significant applications. Medical and human gene therapy research is seen to be revolutionized, where researchers have proposed that this genome editing tool can be used to target and modify "typos" in the three billion letter sequence of the human genome to treat hereditary illnesses like cystic fibrosis.
While Dr. Dounda hopes to see her contribution benefit individuals, she remains involved in a patent dispute. Determining the first to have invented the genome editing technique has been a legal dispute between Dr. Doudna and Dr. Feng Zhang, a Molecular Biologist at Broad Institute who received the Waterman Award for Young Scientists for his work in optogenetics and genome engineering. According to The Broad Institute, the publication by Drs. Doudna and Charpentier from 2012 did not show how to change DNA in cells with nuclei, including human cells—a feat that Dr. Zhang has conducted. So far, the patents have been given to Dr. Zhang.
Despite this battle, Dr. Dounda has maintained her status as one of the co-inventors of the CRISPR-Cas 9 genome editing tool and is recognized as an extraordinary woman who has influenced the scientific landscape and is still adding to it today. Her breakthrough revolutionized genetic engineering as earlier methods were cumbersome, time-consuming, and far from practical.
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