Nordic Life Science 1
was awarded to Emmanuelle Charpentier and Jennife
r Doudna’s discovery of CRISPR/ Cas9 genetic scissors. This enzyme system, which utilizes a very delicate and targeted mechanism to cleave DNA and insert new DNA parts, holds enormous power that affects us all, stated the Nobel Committee for Chemistry announcement. The groundbreaking factor in this discovery is in short that it is so easy to alter genes in a cell. Previously this would take a very long time, it was expensive and precision was low, explains researcher Fredrik Wermeling, PhD, at the Department of Medicine at Karolinska Institutet in Solna. “Within basic research CRISPR has revolutionized the simplicity, for example in identifying genes that affect different biological processes. Within clinical research we are starting to see the first examples of how rare monogenic diseases probably could be cured by using CRISPR to affect the disease-creating mutations. This fundamentally changes how we envision the future of healthcare.” Ever since the molecular structure of DNA was reported in 1953, scientists have been trying to manipulate genes in cells and organisms. Down the years, important findings and advancements have been made, eventually leading to this year’s Nobel Prize and opening the door to this enormous potential to rewrite the code of life. These findings include the discovery of unusual repeated structures common in procaryotes’ genomes containing the same features, suggesting an ancestral origin and high biological relevance, and the introduction of the term for these, CRISPR, Clustered Regularly Interspaced Short Palindromic Repeats. Both the repeats and the spacer sequences between them, remnants of genetic code from past invaders, DNA remnants or DNA scars, gave the scientists more clues and they came to the conclusion that CRISPR was in fact the bacteria’s immune system against virus, and that bacteria had memory. It was discovered that bacteria transcribe these DNA elements into RNA upon viral infection. The RNA guides a nuclease (a protein that cleaves DNA) to the viral DNA to cut it, providing protection against the virus. The nucleases are named “Cas”, meaning “CRISPR-associated”. Fredrik Wermeling, Assistant professor, Karolinska Institutet mmanuelle Charpentier discovered a previously unknown molecule tracrRNA when she studied streptococcus pyogenes, and she showed in 2011 that this molecule is part of the CRISPR/Cas system. Emmanuelle Charpentier and Jennifer Doudna managed to decode the functions of the repeated DNA sequences (CRISPR) together with Cas (CRISPRassociated) proteins. They were able to recreate the bacteria’s genetic scissors in a test tube and the two scientists simplified the molecular components of the scissors so they were easier to use. They had uncovered a fundamental mechanism in a bacterium that causes great suffering for humanity. But it did not stop there, they were also able to reprogram the genetic scissors so that they could cut any DNA molecule at a predetermined site. They demonstrated that RNAs could be constructed to guide a Cas nuclease (Cas9 was the first used) to any DNA sequence. In their game-changing NORDICLIFESCIENCE.ORG 39 PHOTO ERIK HOLMGREN