Last time, we talked ‘small’ but essential. Today will be another episode of a small world. And our story begins in a land of the single-celled animals we call bacteria.
The bacterium is a little guy in the land that has this even smaller mechanism within itself that helps to fight off strangers. Now, I am going to try explaining this mechanism, so stay with me, yeah?
Every organism on our planet has somewhat similar building blocks. And one of these is the nucleic acid. You have probably heard of the deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) already.
You can take the DNA as a sequence of codes that tells every organism what it should grow into, how it should act. And within the bacterium’s DNA is a significant region with two unique contents. One is the repeats of a nucleotide sequence and second are spacers interspersed among the repeating sequences. And these two together form the Clusters of Regularly Interspaced Short Palindromic Repeats, taken in shortened form as CRISPR, pronounced ‘crisper.’
The repeating nucleotide sequences are part of the primary building blocks of the bacteria DNA, but the spacers are of foreign origin, viruses to be exact. Every time a virus invades a bacteria cell, the cell copies the viral genome and incorporates the sequence as the spacer in the CRISPR region. And the function is simple- specificity.
The presence of the spacers helps the bacterium to identify a former enemy virus, thus making its secondary response more effective than its primary/initial response.
How Does the Bacteria Cell Use the CRISPR?
The mechanism is a simple one. The bacterium transcribes the CRISPR region into an RNA sequence that contains contributions from the repeating nucleotides and spacers. We call this the CRISPR RNA (crRNA).
This associate with proteins, such as the cas9 which is an enzyme that is capable of cleaving DNA sequences. And the whole idea is the crRNA (with another RNA called the trans-activating crRNA) lead the cas9 to a specific region of the viral genome with complementary (matching) nucleotide sequence with that copied from the spacer.
Once reached, the cas9 cleaves this sequence from the whole genome structure of the virus, thus stopping its ability to keep growing, and to reproduce. And yay! The virus dies.
So, Why is the CRISPR Important to Us?
Think of being able to cut away a particular undesirable DNA sequence and replace it with a desirable one. That sounds cool, right? Well, Yes! The CRISPR technology allows us this dream come true, and though still rudimentary, shows a lot of promise for future treatment of several genetic diseases.
And How Do We Use the CRISPR?
Also simple! (At least, on paper.)
First, we determine the DNA sequence of the undesirable trait. Then we create an RNA molecule that is complementary to the target gene base pairs. This RNA molecule acts as the crRNA, which we will merge with the trans-activating crRNA sequence to form a complexed ‘guide’ RNA structure.
This Guide RNA will lead an associated protein, cas9 to the exact point of the gene we wish to edit and cut it off. Another safe guide lies adjacent to the target gene. We call this the Protospacer Adjacent Motifs (PAM). Without its presence, the cas9 enzyme will not cut off the gene sequence even though it is complementary to the bases of the guide RNA, thus, improving its accuracy.
Once the enzyme creates a gap, the host cell will try to repair it. And this is where our final hit comes in. We will trick the host cell into replicating a DNA template of our choice, thus replacing the undesirable one or mutated sequence as the case may be. And that ends our gene-editing procedure.
With this technology, we can cure a lot of diseases caused by mutation, right? And not just in medicine, but also food and agricultural sectors have found different uses of CRISPR technology.
However, it is still imperfect in a lot of ways. There is the problem of once-in-a-while off-target cleavages that can lead to further mutation, among others. There are also ethical issues arising from if the act of editing human genomes is justified. What do you think of these ethical questions, though? I’d very much love to read your answers in the comment box below. You know it is a bit boring if I am the only one talking all the time.
Nevertheless, one thing is sure. Ethical issues can only lead to cautions, not total restrictions. Scientists keep working to improve this technology, its accuracy and versatility. And I’m sure in the nearest future, there will be more cures to a lot of diseases.
Anyway, all that said. Isn’t it amazing how essential these small things are? Isn’t the universe in such a beautiful balance? ‘Til next then, Later!