Treating pain with CRISPR

Treating Chronic Pain - Novel Therapy

Pain - mental health

19 to 50% of the world population with chronic pain has debilitating effects on quality of life

Key - Question

What are the novel treatment strategies without any side effects?

Key - Players

You can’t enjoy the pleasant breeze if you are in pain. The sensitive nerves may derail nature’s beauty. The speed with which the pain runs towards the brain is faster than Usain Bolt. By the way, was the speed of pain measured? Interesting question, isn’t it?

There are quite a few pumpkins – aka ion channels along the neuron that open and close to transmit the pain through the spinal cord. Amongst all the pumpkins, Nav1.7 (sodium channel) plays a central part in chronic pain. People with abnormal pumpkins may have extreme effects – too much pain or complete numbness. As most of the pumpkins are similar, some drugs bind to all of them and can’t differentiate bad vs. good, causing side effects including numbness and poor coordination.

So the question is, how do we define specificity? Now a day’s CRISPR has become a synonym for specificity. Just not that, it has become ubiquitous/omnipresent. Present everywhere – Food science, Therapeutics, Diagnostics, Bio-engineering. Maybe we can name all the life science fields.

If you are pre-emptied that CRISPR is used to edit the gene of interest (deletion/insertion) to treat pain – then you are mistaken. We are about to know the usage of CRISPR to modulate the expression of the desired pumpkin epigenetically. Here, in this case – Nav1.7 sodium channel. This means, without changing the gene sequence of the sodium channel, we could modulate the function. To answer your question on how?

You should know that CRISPR has two critical components: A. Cas9 protein which cuts the gene of interest B. gRNA – which befriends the gene of interest and allow Cas9 to cut.

There is a dead Cas9 version of CRISPR (CRISPRi), which does not cut the DNA but remains bound to the gene of interest with gRNA. To this Cas9, we can attach various repressors that temporarily reduce target genes’ expression without permanent change on gene sequence. An example of such a repressor is the Krüppel-associated box (KRAB).

Understand CRISPR as this way – gRNA is like the hand to hold gene of interest. Cas9 is a hungry mouth to chew and cut the DNA, and dCas9 is a stitched mouth that lost the ability to cut. The repressor is a kind of partner that aids in the crime (without affecting the original gene sequence).

The question is how do we introduce this components in cells, for which the researchers use a small inactive virus called adeno associated virus that could shuttle the package into the cells.

After injecting these virus particles into the spine, the mice with chronic pain showed reduced sensitivity with one single injection. The effect was observed for 44 weeks without affecting the expression of other pumpkins (ion channels).

Like CRISPR (after helping to get many awards), the scientists who worked on this experiment are very modest in stating these are preliminary results and need to be taken forward in humans. 

Credits: Read the original article: https://pubmed.ncbi.nlm.nih.gov/33692134/