With the several experimental drugs using a new technology to address COVID-19 via RNA. So what is RNA? Well RNA is Ribonucleic acid (RNA). RNA and Deoxyribonucleic acid (DNA) are perhaps the most important molecules in cell biology, responsible for the storage and reading of genetic information that underpins all life. They are both linear polymers, consisting of sugars, phosphates and bases, but there are some key differences which separate the two acid chains. The differences allow them to work together to fulfil their essential roles.

What are the key differences between DNA and RNA?
Function
DNA encodes all genetic information, and is the blueprint from which all biological life is created. And that’s only in the short-term. In the long-term, DNA is a storage device, a biological flash drive that allows the blueprint of life to be passed between generations2. RNA functions as the reader that decodes this flash drive. This reading process is multi-step and there are specialized RNAs for each of these steps. Below, we look in more detail at the three most important types of RNA.

What are the three types of RNA?

Messenger RNA (mRNA) copies portions of genetic code, a process called transcription, and transports these copies to ribosomes, which are the cellular factories that facilitate the production of proteins from this code.

Transfer RNA (tRNA) is responsible for bringing amino acids, basic protein building blocks, to these protein factories, in response to the coded instructions introduced by the mRNA. This protein-building process is called translation.

Finally, Ribosomal RNA (rRNA) is a component of the ribosome factory itself without which protein production would not occur.

Sugar in DNA and RNA:

Both DNA and RNA are built with a sugar backbone, but whereas the sugar in DNA is called deoxyribose (left in image), the sugar in RNA is called simply ribose (right in image). The ‘deoxy’ prefix denotes that, whilst RNA has two hydroxyl (-OH) groups attached to its carbon backbone, DNA has only one, and has a lone hydrogen atom attached instead. RNA’s extra hydroxyl group proves useful in the process of converting genetic code into mRNAs that can be made into proteins, whilst the deoxyribose sugar gives DNA more stability.

Bases
The nitrogen bases in DNA are the basic units of genetic code, and their correct ordering and pairing is essential to biological function. The four bases that make up this code are adenine (A), thymine (T), guanine (G) and cytosine (C). Bases pair off together in a double helix structure, these pairs being A and T, and C and G. RNA doesn’t contain thymine bases, replacing them with uracil bases (U), which pair to adenine1.

Structure
Whilst the ubiquity of Francis Crick and James Watson’s (or should that be Rosalind Franklin’s?) DNA double helix means that the two-stranded structure of DNA structure is common knowledge, RNA’s single stranded format is not as well known. RNA can form into double-stranded structures, such as during translation, when mRNA and tRNA molecules pair. DNA polymers are also much longer than RNA polymers; the 2.3m long human genome consists of 46 chromosomes, each of which is a single, long DNA molecule. RNA molecules, by comparison, are much shorter4.

Location
Eukaryotic cells, including all animal and plant cells, house the great majority of their DNA in the nucleus, where it exists in a tightly compressed form, called a chromosome5. This squeezed format means the DNA can be easily stored and transferred. In addition to nuclear DNA, some DNA is present in energy-producing mitochondria, small organelles found free-floating in the cytoplasm, the area of the cell outside the nucleus.

The three types of RNA are found in different locations. mRNA is made in the nucleus, with each mRNA fragment copied from its relative piece of DNA, before leaving the nucleus and entering the cytoplasm. The fragments are then shuttled around the cell as needed, moved along by the cell’s internal transport system, the cytoskeleton. tRNA, like mRNA, is a free-roaming molecule that moves around the cytoplasm. If it receives the correct signal from the ribosome, it will then hunt down amino acid subunits in the cytoplasm and bring them to the ribosome to be built into proteins5. rRNA, as previously mentioned, is found as part of ribosomes. Ribosomes are formed in an area of the nucleus called the nucleolus, before being exported to the cytoplasm, where some ribosomes float freely. Other cytoplasmic ribosomes are bound to the endoplasmic reticulum, a membranous structure that helps process proteins and export them from the cell.

The Experimental COVID 19 drugs as noted above uses Messenger RNA (mRNA). Normally these experimental drugs go through long trials to determine both short and long term impacts. Thus in the United States, in order to receive Food and Drug Administration approval, the companies will have to prove there are no immediate or short-term negative health effects from taking the experimental drug. But when the world begins inoculating itself with these completely new and revolutionary vaccines, it will know virtually nothing about their long-term effects.

Some are questing this rush for using experimental drugs without understanding all the risk such as the following:

“There is a race to get the public vaccinated, so we are willing to take more risks,” Tal Brosh, head of the Infectious Disease Unit at Samson Assuta Ashdod Hospital, told The Jerusalem Post.

When Moderna was just finishing its Phase I trial, The Independent wrote about the vaccine and described it this way: “It uses a sequence of genetic RNA material produced in a lab that, when injected into your body, must invade your cells and hijack your cells’ protein-making machinery called ribosomes to produce the viral components that subsequently train your immune system to fight the virus.”

“In this case, Moderna’s mRNA-1273 is programmed to make your cells produce the coronavirus’ infamous coronavirus spike protein that gives the virus its crown-like appearance (corona is crown in Latin) for which it is named,” wrote The Independent.

Tal Brosh, head of the Infectious Disease Unit at Samson Assuta Ashdod Hospital, said that this does not mean the vaccine changes people’s genetic code. Rather, he said it is more like a USB device (the mRNA) that is inserted into a computer (your body). It does not impact the hard drive of the computer but runs a certain program.

But he acknowledged that there are unique and unknown risks to messenger RNA vaccines, including local and systemic inflammatory responses that could lead to autoimmune conditions.

A paper from the Penn Medical Center for Evidence-based Practice in December 2020 noted the following Evidence Summary:

EVIDENCE SUMMARY

• There are no specific guidelines for use of messenger RNA (mRNA) vaccines or contraindications to mRNA vaccines.

• No large trials of any mRNA vaccine have been completed yet.

• The only evidence on safety of mRNA vaccines comes from small phase I and phase II trials of SARS-CoV-2 vaccines, with
  follow-up typically less than two months.

• Systemic adverse events such as fatigue, muscle aches, headache, and chills are common.

• Severe systemic adverse events were reported by 5 to 10 percent of trial subjects.

• Localized adverse events such as pain at the injection side are common.
  Both systemic and local adverse events usually are resolved within one or two days.

• The rate and severity of adverse events appears to be higher for the second dose of vaccine than for the first.

• Higher vaccine doses appear to increase the rate and severity of adverse events.

• Larger trials of SARS-CoV-2 vaccines are in progress, with results expected in mid-2021.

• There is not sufficient evidence to support any conclusions on the comparative safety of different mRNA vaccines.

• Direct evidence on the comparative safety of mRNA vaccines and other vaccines is lacking.

Thus, there is much to learn using new approaches like mRNA. For now these are all experimental and know one knows what the short and long terms effects on the human body due to this new approach.

As they used to say in the news a long time ago, "Stay tuned".

References
https://www.ncbi.nlm.nih.gov/books/NBK21154/
https://ghr.nlm.nih.gov/primer/basics/dna
https://www.rnasociety.org/about/what-is-rna/
https://www.nature.com/scitable/topicpage/chemical-structure-of-rna-348
https://www.genome.gov/25520880/deoxyribonucleic-acid-dna-fact-sheet/#al-2
http://jcs.biologists.org/content/126/21/4815
https://www.jpost.com/health-science/could-an-mrna-vaccine-be-dangerous-in-the-long-term-649253