Why Researchers See Its Potential in Pharmaceutical Biotechnology & Agriculture
What is RNA, and What’s the Difference Between RNA & DNA?
RNA is short for ribonucleic acid. It is a polymeric molecule essential in various biological roles such as the coding, decoding, regulation and expression of genes.
RNA and DNA (deoxyribonucleic acid) belong to a group of macromolecules called nucleic acids. Along with lipids, proteins, and carbohydrates, they constitute one of the four major macromolecules essential for all known life forms.
The most noticeable difference is that while DNA is double-stranded, RNA is single-stranded. Its backbone comprises alternating sugar (ribose) and phosphate groups. Attached to each sugar is one of four nucleotide bases: adenine (A), uracil (U), cytosine (C), or guanine (G). Similarly, the backbone of each DNA strand is the alternating sugar (deoxyribose).
The Significant Role of RNA in All Life
We all know that the DNA carries genetic instructions (or blueprint) for the development, functioning, growth and reproduction of all known organisms. How are these instructions transferred or expressed? How are they regulated?
DNA is often described as the building block of life but is essentially a database of information cells need to create proteins. RNA are the ones that do the work of creating proteins. They are the pivotal ‘molecule of life’, involved in almost all aspects of cell biology.
The Many Types of RNAs
When it comes to protein synthesis (a core biological process in all life), there are three main types of RNA – messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).
- mRNA – short for messenger RNA, these strands are transcribed from the DNA and attaches to the cell ribosomes (sites of protein synthesis). A strand of mRNA is typically composed of codons (each codon is a set of three nucleotide bases). Believe it or not, mRNA accounts for just 5% of the total RNA in the cell.
- tRNA – short of transfer RNA, these molecules carry amino acids (building blocks of proteins) to ribosomes to synthesize proteins. Each amino acid corresponds to a codon on the mRNA.
- rRNA – short for ribosomal RNA, these molecules (together with certain proteins) are subunits that make up the ribosome. They are responsible for translating an mRNA strand into its designated protein.
With the above three types of RNA working in parallel, our cell ribosomes can synthesize proteins.
That’s not all, several more varieties of RNA exist, and they are involved in post-transcriptional modification, DNA replication, as well as gene regulation.
Use of RNA in Vaccines
Pfizer’s Comirnaty and Moderna’s Spikevax are currently the more prominent coronavirus vaccines that harness the potential of mRNA. Developed in 2020 to combat the COVID-19 pandemic, these vaccines indicate just one of the near-infinite possibilities that RNA technology can offer in life sciences.
While the concept of mRNA vaccines sounds relatively advanced, it dates back to 1995, when researchers designed the first mRNA vaccine that encoded cancer antigens. In 2009, researchers conducted the first-ever trial on cancer immunotherapy using mRNA vaccines in human subjects with metastatic melanoma (a type of skin cancer). The trial showed an increase in the number of vaccine-directed T cells against melanoma.
Use of RNA in Therapeutics
Further research in RNA-based therapeutics could open the door to new treatments for diseases like cystic fibrosis, cancer and HIV. With the apparent success of the COVID-19 vaccines, such applications may soon be realized.
In recent decades, ongoing research includes the use of RNA interference to target a sequence in the hepatitis C virus for destruction, suppressing HIV replication in macrophages, as well as the use of RNAi-mediated gene silencing in humans for the treatment of skin cancer melanoma.
Most RNA therapies can be sorted into one of 3 broad categories:
- Those that target nucleic acids (either DNA or RNA)
- Those that target proteins
- Those that encode proteins
There are emerging hybrid approaches that combine several RNA-based mechanisms into a single package.
The first RNA drug approved by the US Food and Drug Administration (FDA) was Pegaptanib (back in 2004) for treating a form of age-related macular degeneration (AMD) where blood vessels penetrate the retina. Following pegaptanib, a few other drugs were approved by the FDA for the treatment of rare diseases over the course of the next decade. These include inotersen & patisiran for treating nerve damage and nusinersen & eteplirsen for treating neuromuscular diseases.
Such novel drugs are considered as a leap forward in therapeutics as they would help the patients’ bodies to remedy the root cause of such disorders on their own. For example, pegaptanib uses RNA aptamers that would bind to the troublesome proteins, blocking unwanted growth, thus preventing blood vessels from penetrating the retina. Eteplirsen tackles the Duchenne muscular dystrophy by using antisense oligonucleotides (ASOs) to block portions of unwanted genes, resulting in only functional proteins being translated and synthesized.
Use of RNA in Agriculture
In recent years, RNA-based solutions have shown potential in providing farmers with effective pest control. Worldwide, an estimated 20-40% of crop yield is lost to pests and diseases every year, hindering progress in several of the United Nations’ Sustainable Development Goals.
Many destructive insects, weeds, viruses and fungi have developed resistance to pesticides. Farmers have fewer options for pest control.
Greenlight Biosciences has recently developed an RNA-based solution that can be applied to a plant. It would then silence a specific gene in the pest that is critical to its growth. All this is done without any genetic modifications. One example is a dsRNA (double-stranded RNAs) product that can target a specific pest via RNA interference. It has been tested in over 20 crop fields.
The pest within the immediate area is eliminated, and the plant stays healthy without any negative impact on the environment.
Conclusion
While DNA is essentially a database of information cells need to create proteins, RNA is the pivotal ‘molecule of life’, involved in almost all aspects of cell biology.
The COVID-19 pandemic and the recently approved mRNA vaccines have brought RNA technology into focus, with potential applications in more vaccines and therapeutics against other diseases (rare or common). Recent discoveries have led to the use of RNA as an effective biocontrol for crops, with minimal impact on the environment.
Sources:
- https://www.nature.com/articles/d41586-019-03068-4
- https://www.news-medical.net/life-sciences/-Types-of-RNA-mRNA-rRNA-and-tRNA.aspx
- https://www.wbur.org/commonhealth/2021/01/11/modified-mrna-future-treatments
- https://the-dna-universe.com/2021/04/15/the-history-of-mrna-applications/
- https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-once-dismissed-idea-became-a-leading-technology-in-the-covid-vaccine-race/
- https://www.jenabioscience.com/rna-technologies
- https://www.springer.com/gp/book/9783642121678
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551859/
- https://www.theatlantic.com/ideas/archive/2021/03/how-mrna-technology-could-change-world/618431/
- https://en.wikipedia.org/wiki/RNA
- https://en.wikipedia.org/wiki/DNA
