CRISPR CAS-9, The Genetic Programmer.
Whenever we buy any gadget or equipment or machinery, there comes an instruction manual along with it, which helps us understand how it works. We, human beings are also a big complex set of machinery and our instruction manual is our genome.
What if I were to tell you that you can now alter your genome and make any changes that you want? Just like Spiderman, inserting the spider genes into our DNA and boom! Superhuman powers! Well, this sci-fi isn’t fiction anymore, thanks to Emmanuelle Charpentier and Jennifer Doudna for their work on CRISPR CAS-9, which is a new, fast, cheap, and relatively easier gene-editing tool.
But, What is CRISPR CAS-9?
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, which simply means- a short DNA segment with repeating base sequences. These are naturally found in prokaryotes, where they defend the organism from viruses. CAS-9 is a CRISPR-associated protein that very precisely chops off the DNA and alters the genes.
How does it work?
The human immune system consists of twenty-one different kinds of cells and two proteins. We have very sophisticated immune response mechanisms, one of which is a memory-based, adaptive/ acquired immunity. Based on what is taught in old warfare, knowing your enemy is the key to victory. our bodies are equipped with cells that can remember and recognize the enemy flags (antigens) and provide an army of soldiers (antibodies) to fight the enemy when they attack again, with an even faster and stronger offense. Scientists discovered that bacteria also have an adaptive immune system, but with different underlying mechanisms than humans.
In prokaryotes, CRISPR works like an archive, they store the genetic code of the viruses. These codes are then copied into RNAs which form a complex with CAS-9 proteins (RNA-guided DNA cutter). CAS-9 proteins are like scouts, who are given the genome sequence of the fugitives. And then in the future, when the virus infects again, CAS-9 protein identifies them and cuts off their DNA, making them useless.
The good news for us is that the CRISPR system is programmable. Scientists create a guide RNA, which resembles the gene they want to edit and then they attach it to CAS-9. CAS-9 will then find the target gene and chop them off.
For example, every year, 3 lakh children are born with sickle cell disease, which is caused by defective hemoglobin. It is a recessive autosomal genetic disorder. Scientists recently treated a sickle cell disease patient by using the CRISPR tool, a treatment named CTX001. They caused the deletion of the BCL11A gene, which in turn resumed fetal hemoglobin synthesis by reactivating the HBf gene. The idea was- restoring the fetal hemoglobin synthesis could compensate for the defective hemoglobin, leading to a remarkable reduction in the occurrence of anemia, and the scientists were absolutely successful! (YAYY!!!)
But, as you know, nature fights back! phages have developed over time- Anti-CRISPRs. They inhibit CAS-9 and thereby protect their DNA from getting chopped off. Scientists found out that one of the anti-CRISPR proteins, AcrIIC1, traps CAS-9 and has the ability to block DNA cutting. If we can harness and manipulate this mechanism, it could do wonders from a technological application standpoint.
CRISPR editing works for all types of cells- microorganisms, humans, animals, and even plants.
The technology would help us cure HIV infections, cancers, and thousands of genetic diseases in the near future. Also, a lot of scientists across the globe are researching using CRISPR tools on human embryos and they have been partially successful, which means- genetically modified humans are just a decade away from us.
In the words of Jennifer Doudna,
If you think about it, it is really a profound thing, because it really gives humans the power to control the evolution of organisms in our environment and also potentially our own evolution in a very targeted manner. It also evokes a sense of caution and respect for this powerful technology.
In conclusion, CRISPR CAS-9 gene-editing tool works similarly to a genetic programmer, one that hacks into our genetic codes, fixes mutations, augments characteristics that already exist, and even adds new features, thereby contributing to a better future for humans, animals, and plants.
What would you use CRISPR gene-editing tool for?
