Functional Mosaicism could Shape the Future of Therapeutics

Cells that appear identical may use different proteins for the same tasks. A University of Maryland led research has discovered Functional Mosaicism throughout the body.

Functional Mosaicism means identical cells use different paths to perform the same function.

These findings can prove pivotal for therapeutic treatments. Treatments targeting a specific molecule will have to consider the Functional Mosaicism. This might be the reason for the ineffectiveness of Medication. Particularly those which target a gene that produces a specific molecule.

The journal: Nucleic Acids Research showcases the findings from the research.

Rendering medications ineffective

Therapies targeting cell processes depend on the proteins involved. But, if the targeted cells are not producing what is being targeted the medication won’t work. This might answer the relapses of diseases like cancer.

Such treatments might not work where the cells work in a different style.

Different cell behaviors in different locations were already known. But, researchers assumed similar cells sourced from the same tissue to work identically.

Functional mosaicism possesses the potential to deceive. The administered drug might look as if it worked. mostly because it worked in most if not all cells. The unaffected ones employed a different operational model and maybe the reason for a relapse.

The analyzing RNA interference (RNAi) helped discover the functional mosaicism. This finding is in line with the level of variability found in prior studies. The team suggests that the variable results obtained previously might be due to the same reason.

During the study, the team was analyzing RNA’s gene control function (RNAi). The body cells can recognize double-stranded RNA. This allows them to turn off genes with matching DNA sequence.

The RNAi Functionality

RNAi relies on RNA polymerases (RdRp). RdRps replicate strands of RNA that can isolate and ‘silence’ their matching genes.

Various RdRp enzymes exist, but researchers assumed they were tissue-specific. Meaning all cells from a tissue used the same RdRp enzyme to carry out RNAi.

Firstly, the team first modified nematode worm genes to fluoresce green. Further, they altered the worms to produce double-stranded RNA. The modified RNA roamed the bodies and silenced the gene for green fluorescence. This was successful in many cell types, including intestinal cells.

Then the researchers removed the RdRp thought to be responsible for RNAi. Researchers then analyzed the Gene silencing in the intestinal region.

Only some cells fluoresced green. This meant something continued to silence the fluorescent gene in other intestinal cells.

The removed enzyme called RRF-1 was not the only RdRp in the species of worm. It had 3 others.

Read also – World’s First Gene Edited Born Twins Got Scientists Worried

Removal of RdRps, one at a time, helped in finding the culprit. The EGO-1 RdRp thought to aid in RNAi only in reproduction-related germline cells was the one.

The random nature of enzyme effectiveness

Repeated experimentation showed that some cells needed RRF-1 for silencing. In contrast, others used EGO-1 to the same effect. There was no definitive pattern to show which cells used what RdRp.

Diseases aren’t adapting to medicines. They already have another way to carry out what they do.

Treatments must account for the alternate ways cells function to affect them. The team suggested that evolution might have played a role in this.

A cell might know many different ways to carry out a function. But along the way different sets of cells stuck to a single specific way. Which cells went into which places, it is almost impossible to predict.

The study answers the antibiotic resistance and cancer relapses. Further, it paves the way for tailoring therapeutic treatments to cover all possible RdRps. This would ensure effectiveness and might save countless lives each year.

Adeena Tariq

Adeena's professional life has been mostly in hospital management, while studying international business in college. Of course, she now covers topics for us in health.

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