A Future Perspective for mRNA, SARNA and Circular
When mRNA plasmid, vaccines started rolling out in the late 2020s to combat the COVID pandemic it was the first time that a large-scale application of the molecule followed many years of research.
But the effectiveness of these vaccines was just the first step.
In the relatively brief timeframe required to create the COVID vaccines and COVID vaccines, the mRNA plasmid field has probably advanced by as much as 10 years more quickly than what would be the case.
The breakthrough has fueled excitement for research. This will eventually include self-amplifying the RNA (saRNA) as well as circular DNA. It could allow making another jump within 5 to 10 years.
As an aspiring scientist, I am aware of the potential in all three of them to create treatments. We can provide more therapies to our patients, and also help them to receive vaccinations to fight diseases more effectively.
The growing number of RNA options will allow more options to create those treatments. The use of mRNA has resolved many of the problems the industry has faced in the past with proteins and DNA.
This is the reason for the increasing interest in the use of RNA.
mRNA Begins, saRNA Follows.
Beginning with mRNA plasmid and the saRNA, mRNA has a more established background and is the reason each of Moderna and BioNTech utilized it to develop their vaccines, besides the fact that they’ve been working within the mRNA area for quite some time.
In contrast, self-amplifying is in its infancy and does come with some drawbacks.
SaRNA is a massive molecule that is at least 8kb in length. The T7 polymerase is not very efficient in generating the transcripts that you need, so you will get transcripts that are truncated.
Furthermore, RNA that is larger tends to be less stable. It is essential to be cautious about downstream manufacturing processes to ensure that you do not degrade lots of the RNA.
From a regulatory standpoint, We’re still trying to determine exactly how our immune system could respond to the replicase part in general.
Despite those challenges, however, there have been positive results from saRNA-based trials. For instance, HDT Bio recently received an Emergency Use Permit in India for its COVID-19-based saRNA vaccine.
This HDT approval highlights an important advantage of saRNA compared to mRNA dosage sizes. In theory, it is possible to give a 50-100-fold lower dose with saRNA contrasted to mRNA.
When you look at the areas for vaccines and dose sizes, reducing the dosage allows vaccines to be more easily accessible, particularly for poorer nations. I believe that this highlights the potential of the saRNA.
In addition, the molecules offer lots of space to improve their development. It is possible to tweak them in order to reduce some negatives, such as the size.
A thing to be aware of is that it’s a big undertaking to create saRNA to treat diseases or even to prove its safety.
mRNA plasmid is a step ahead in comparison to saRNA and after we’ve managed to make use of mRNA in therapeutics that work I believe that saRNA is the next step in the field of RNA.
In the future, we’ll likely add circular RNA to the mix.
Circular RNA is in the Wings
To my view, Circular RNA will take five to 10 years at the very least before it reaches the clinic, however, there are some positives worth considering. Circular RNA is far more stable due to its circle.
It’s much more active than circular RNA (per unit of mass, or copy) This means that it can result in much greater protein expression. However, its IP landscape is uncertain.
In this regard, it is important to be cautious with circular the RNA.
However, it also has lots of advantages. For instance, you do not require an RNA cap. It’s enough to create the RNA.
After that, you must cleanse it to eliminate the linear fragments, or it could trigger the immune system to produce.
Of the three options, mRNA is on the way and is already in use self-amplifying RNA could be five years away from the widespread application, and circular RNA is a good 10 years further away.
However, as it pertains to circular RNA it could open all the possibilities of therapies. If you don’t need to cap it, especially if it’s circular, then it will trigger less immunogenicity from an uncapped mRNA standpoint.
This is the benefit of circularity. In the future, there are difficulties. However, I believe that circular RNA will be the molecule that will be employed within 10 to 15 years from the present.
There are no data from humans since it’s not available to humans yet. However, the first evidence of the concept of AAV cell line data appears very promising for circularity.