Recent Study Indicates Tiny Molecule Medications Can Target RNA, Opening New Avenues for Illness Therapy

Most drugs for the management and cure of human illness have targeted proteins up until now.

RNA has been thought to be too volatile to address with pharmacological treatment by medication makers.

Moreover, a screening of 50,000 chemicals indicated drug-like action against an RNA prototype known as Xist, paving the way for novel therapeutic development.

RNA in creating new possibilities for treatment of disease

RNA (ribonucleic acid) is involved in many aspects of people's wellbeing, and a new study published in the journal Nature provided compelling evidence that RNA might be a promising pharmacological target.

This study, conducted by Massachusetts General Hospital (MGH) experts, revealed that a new class of biological variables with tens of thousands of members may be targeted, ushering in a new era in medication innovation.

Among the over 20,000 individual proteins involved by the Human Genome Project, nearly all presently marketed medications target one of about 700 disease-related enzymes.

However, there is now a growing interest in including RNA in the roster of "druggable" targets in recent years.

The genetic makeup for creating proteins is carried by DNA (deoxyribonucleic acid) in cells.

A piece of DNA is replicated into a "coding" RNA, which would then be interpreted into protein.

However, noncoding RNA makes up the great bulk of RNA in the human genome, or about 98%.

According to Jeannie Lee, MD, PhD, of MGH's Department of Molecular Biology, "these noncoding RNAs serve extremely significant roles in the genome, and we now understand that mutations in this noncoding region can result in illness," as per ScienceDaily.

And it's possible that there are significantly more RNA genes than protein-coding genes.

If we could target these RNAs, the number of medications we could identify to treat people would vastly rise.

The pharmaceutical industry, on the other hand, has been reticent to approach RNA as a medication target in the past.

Drugs attach to proteins like a key in a lock, and proteins have stable forms or conformations, making them ideal targets.

RNA, on the other hand, is very flexible, or "floppy," and capable of taking various conformations, according to Lee.

Because of the instability of noncoding RNA, pharmaceutical companies have been hesitant to invest in developing drugs that target it.

Although all of this shape-shifting, some areas of RNA are known to maintain stable configurations, but locating these regions has proven difficult.

Status of RNA-targeted Ligands

Up until 2012, attempts to find small-molecule ligands for RNAs mainly recognized extremely basic (and thus electrostatic attraction under physiological circumstances) and planar particles capable of complexation between stacking on RNA bases, according to well-researched classic reviews on RNA-targeted small molecules.

These compounds have a high affinity for RNA but a limited specificity for it.

The pharmacological characteristics of these compounds are frequently weak, with minimal cellular absorption and considerable toxicity.

As a result, most of the early research was focused on compounds having qualities that were definitely non-drug-like.

Many organizations are currently working on techniques that utilize methodologies likely to uncover compounds with realistic drug-like qualities, since the area of RNA-targeted ligand discovery is quickly developing.

The surviving motor neuron protein (SMN2) pre-mRNA, the HIV-1 transactivation response (TAR) bulged helix, and the myotonic dystrophy type 1 (DM1) CUG triplet repeat are only a few of the components in this category, and some of them have the same targets.

However, this collection fits the actual state of the research and serves as a good preliminary step for considering ideas for addressing RNA with small molecules selectively and effectively.