CRISPR/Cas: history, present and future

On the occasion of two female professors receiving the Nobel Prize in Chemistry in 2020 for what is considered the greatest discovery of the 21st century: the gene editing tool CRISPR/Cas, I would like to write about my insights during 3 years of work. with CRISPR/Cas for everyone to read and discuss.

1. History of CRISPR/Cas discovery

2. Mechanism of action of CRISPR/Cas

3. Real-life visual example of the CRISPR/Cas process

4. The explosion of the CRISPR/Cas system in cancer research

5. Application of CRISPR/Cas system in thalasemia disease

6. Application of CRISPR/Cas system in rare and future genetic diseases

Part I: History of CRISPR/Cas discovery

There was a professor who said in front of a medical student hall in the US that "I would be shocked if you guys sitting here don't know about CRISPR/Cas and why the CRISPR/Cas discovery is considered the greatest in the 21st century." ”. So in the simplest way possible, I will introduce to you the history of discovery and the mechanism of action of the CRISPR/cas system. The research process to invent the CRISPR/cas system is the result of a series of small to large successes of research from 1987 to early 2013 by many scientists, the process of fundamental research. version as follows:

You may be surprised because this technique comes from basic research on how bacteria can resist virus attacks. Once the virus has penetrated into the VK, the multiplication and attack of the virus is likened to a bomb. You probably already know its danger through major pandemics or the latest covid-19 on the planet. People.

Therefore, the attack of phage (a type of virus that specializes in invading and multiplying in VK and ancient VK cells) is a huge challenge to the existence of VK and VK has developed many mechanisms to resist this attack. phage infection. A widespread system to combat such dangerous foreign DNA molecules is the CRISPR/Cas immune system, found in 48% of bacteria and 95% of archaea, whose effect is to recognize foreign agent and destroy it. So what is CRISPR? In 1987, a research group from the research lab of Professor Yoshizumi Ishino at Osaka University in Japan found strange gene segments 29 nucleotides long that were repeated many times and separated by long spaces or spaces. about 32 other nucleotides in the DNA sequence. At that time, because gene sequencing techniques were still difficult, explaining it was a challenge. By 2002, Professor Ruud Jansen's research group at Utrecht University, the Netherlands named this "spaced repetitive arrangement sequence" CRISPR - Short for "Clustered Regularly Interspaced Short Palindromic Repeats". ”. Furthermore, they also identified that the CRISPR sequence is always accompanied by a number of genes distributed nearby, called Cas genes, with the ability to encode enzymes that cut DNA. But to explain in depth, three years later, a group of scientists announced discoveries that clearly explained the mystery of this CRISPR chain, especially the discoveries of two scientists Doudna and Capentier in late 2012 and early 2012. In 2013, they confirmed that it is an active mechanism to fight against virus attacks by using this Cas enzyme to cut pieces of the virus's genes and then automatically attach those gene sequences to their own gene segments and separate them. with spaces.

Therefore, CRISPR sites contain many short repeat sequences of about 20-30 base pairs, separated by different spacer sequences or spaces of similar length, often similar to segments of the genome. Bacteriophage genes or other genetic elements that retain small pieces of viral DNA from successful battles. This CRISPR segment is then copied in large quantities into small CRISPR RNAs (crRNAs) that are then formed into complexes with Cas proteins. Cas enzyme acts as a gene editing machine with a special way of searching, identifying, then cutting and destroying genes with corresponding DNA segments integrated in the CRISPR sequence, allowing scientists to Delete or add a small piece of DNA as desired into the cell.

This gene editing application has been successful in mice, monkeys, and human embryos. Scientists in Philadelphia have shown that they can use CRISPR to cut out the DNA segment that the HIV virus has integrated from infected human cells. Most recently, a world-famous incident caused three Chinese scientists to be imprisoned and fined a huge amount of money for using this system for their own purposes in violation of medical ethics, they guarantee. that it is possible to produce completely HIV-free children from HIV-infected parents. At least 8 children have been created from this laboratory and now these children are still under observation and details have not been announced. There are many other good stories surrounding CRISPR/Cas, but I would like to stop the first article here because it is already quite long. In short, in just 8 years from the beginning of 2013 until now, the CRISPR/cas system has been applied extremely widely in many fields, especially medicine, agriculture, and pharmaceuticals. I can't even imagine them