RNA based therapeutics have the potential to revolutionize Health Care. By being able
to treat diseases at the source of the problem,
RNA-based therapeutics have the potential to not only treat many
different types of diseases,
but also cure them.
This is possible,
because rather than targeting symptoms,
these therapies are instead targeting the causative agents or the
pathways of the disease.
So, what are our new therapeutics and how do they
prevent and cure diseases? RNA is a single
strand of genetic material within the cells.
It is made from DNA and is the link between
DNA and proteins.
It carries the instructions from DNA to RNA,
and then cellular machinery found within the cell
which makes the proteins.
The main function of RNA is to create proteins and
DNA. RNA plays a role in the number of proteins
made, and regulates the expression of production of certain types of
protein. Proteins control
most processes within a cell and therefore controlling RNA
gives us a way to control proteins,
and as a result, control processes.
We can already see how we can target various parts
of the cell to change the conditions and therefore the
state of the disease.
There are various types of RNA that can each be used
in the unique ways to target and regulate different from
the processes in the cell.
mRNA or messenger RNA is the blueprint that is read
by cellular machinery
to create proteins from.
And as a result.
we can target messenger RNA as most proteins are made
from them.
mRNA can also be used as RNA Therapy, as
we are all familiar with the Covid-19 vaccine,
which is an mRNA-based vaccine.
And this RNA technology is very useful, it works by
introducing lab-synthesized mRNA into a cell, and a cell
will start producing a protein of interest.
This can help us create vaccines
like we have encountered.
It can also help us create therapies for rare,
genetic diseases,
and cancer.
siRNA or small interfering RNA binds to the mRNA that
produces the protein and breaks it down, resulting in lower
production of specific proteins.
siRNA is usually found in viruses,
not in mammals.
It also targets one mRNA target. As you can imagine,
this makes it a perfect candidate for the use in RNA
therapy. miRNA or microRNAs is present in all animals
and plants.
And as a result, plays many roles within
all cells of our bodies. It can increase the production
of proteins or decrease
the production of proteins in various ways.
One piece of miRNA
also can affect multiple mRNAs and as a result, control
multiple proteins.
miRNA plays an important role within
all aspects and functions of ourselves.
And therefore,
our bodies.
This is why it isn't a good target for RNA
therapy yet.
But once we
have a better understanding of the relationships between
different types of miRNA and their roles within certain pathways,
it may become a much more viable option.
As you can see,
these various methods of RNA therapy,
all have to do with altering
the production of proteins that are responsible for different roles,
and since proteins are extensively used for various purposes,
we can easily control most functions and therefore,
target different proteins responsible for different diseases.
At this point in time,
there's a lot of research being done around how RNA
therapeutics, can be used to treat a variety of
diseases.
One such example, is that of the treatment of HIV.
HIV, which stands for Human Immunodeficiency
Virus,
is a virus that attacks the body's immune system.
This can eventually lead to the development of AIDS,
which has a prognosis of less than 10 years.
One study done by Song and other researchers found that
siRNA could induce potent gene splicing by degradating the HIV
mRNA.
It was determined that the siRNA could induce long-lasting HIV
inhibition in macrophage cells.
Macrophage cells are an especially important target as macrophages
replicate large amounts of the virus.
Thus, the siRNA were not only able to prevent infection
in primary macrophages,
but also suppressed viral replication fallowing infection.
Additionally,
literature by Bobbin and others researchers provide an overview of
RNA based therapies for HIV-1
In this review,
they discussed how siRNA and short hairpin
RNA can target specific sequences within
HIV-1 RNA.
Ultimately,
RNA silencing blocks key steps in the viral
replication, cycle.
Inhibiting viral replication.
This would be a safer and more effective treatment of
HIV, as RNA
therapeutics can compensate for viral mutants.
RNA Therapeutics also have the potential to treat cancer such
as melanoma.
Melanoma is a type of skin cancer in which malignant
cancer cells
develop from melanocytes, a part of the epidermis spread across
the organ.
These cancer cells can spread to other areas of the
body, through the lymph system,
or blood. A study done by Davis and other researchers
discusses a human Phase 1 clinical trial
of systemic administration of siRNA to patients with melanoma.
The data demonstrated that the siRNA could produce gene inhibition
and these with subsequent productions in the skin cancer mRNA
in protein.
Although the discovery of RNA-based Therapy is
groundbreaking, there are a few challenges that still need to be addressed.
RNA is naturally unstable.
Additionally,
RNA-based Therapeutics can invoke an immune response.
These two factors of challenges to RNA-based Therapy
as the body reacts against therapy inserted.
RNA is susceptible to degradation
by nucleases once is injected into the body.
As a result,
the delivery of RNA to specific target cells has been
the biggest challenge for RNA based therapeutic approaches.
Bo Rode Hansen,
the chief executive of Genevant Sciences, says
"the problem of RNA
therapeutic has always been delivery". Due to the variety of
organ and tissue types within the body,
the challenges with the delivery of therapeutics becomes amplified.
Kevin Fitzgerald,
senior vice president of research at
Alnylam Pharmaceuticals, states
"Each organ is a little bit different and the challenges of
delivery are a little bit different". As we go into
each new organ,
there will be some learning to do.
Additional challenges due to RNA's degradation are the need
for repeated regular doses of therapeutics and the maintenance of
active doses in the body. As RNA degradation
occurs, the therapeutic approaches need to be reapplied periodically in order
to be sustained. The active doses within the body must
be maintained as well to carry out the therapy for
as long as possible without degradation.
With the presence of these challenges,
Wim Tiest, a special adviser at the company
eTheRNA advised
that through careful
selection of targets that require short interventions,
the full benefit of RNA-based therapeutic approaches can be provided.
The more research that is done on how to overcome
these challenges, the more effective RNA-based therapeutic approaches can be.
With the ongoing developments in the RNA Therapeutics,
the next frontier seems to be its use in personalized
medicine. That is, the tailoring of medical treatments to the individual
characteristics of patients. As an approach to Medicine, personalized medicine
relies on understanding the genetic and other biochemical differences between
individuals in order to make decisions about what treatment plans
they should receive.
RNA Therapeutics may be useful in this field because
they allow us to target a specific cause of a
disease at the cellular level.
For example,
many forms of cancer originate from mutations in genes that
normally control the ability for cells to divide.
When these genes are muted,
the proteins that they encode,
may become defective and lose the ability to control cell
division,
causing cells to divide uncontrollably,
and this may lead to the growth of tumors and
development of cancer.
If we could identify what mutation was causing this problem,
or even the protein involved we could design or use
an RNA therapy that restores the function of that
gene or supplements,
the cells so that they can still produce the protein
needed to control cell division.
This approach may become more favorable than other existing approaches
such as chemotherapy or radiation therapy,
which often harms neighbouring cells in addition to the target
cells.
Additionally,
the same disease
may have a different underlying cause in two different people,
which could explain why certain treatments may work better for
some people and not for others.
With an RNA therapy treatment to be designed
or chosen to specifically address
the genetic defect present in a specific individual.
This could increase the likelihood of successful treatment of the
disease as well as reduce risks
of unwanted side effects. To conclude RNA therapeutics are
continuously evolving.
And as the technology progresses,
they hold a strong potential to become a very valuable
tool in the future of medicine.
If you would like to learn more about RNA
Therapeutics,
feel free to check out some of our recommended videos
and resources in the description below.