RNA Therapeutics
Infographic
Last Updated: January 16, 2024
(+ more)
Published: December 5, 2023
|
Molly Coddington
Senior Science Writer
Molly Campbell is a senior science writer at Technology Networks. She holds a first-class honors degree in neuroscience. In 2021 Molly was shortlisted for the Women in Journalism Georgina Henry Award.
Learn about our editorial policies
Credit: Technology Networks
From mRNA vaccines to RNA interference (RNAi) and beyond, discover how RNA therapeutics are reshaping the landscape of genetic medicine.
Download this infographic to learn more about:
- What RNA therapeutics are
- The different types of RNA therapeutics
- How RNA therapeutics are developed
- The present and future landscape of RNA therapeutics
RNA
RNA
RNA therapeutics are a class of biopharmaceuticals that use RNA to treat or prevent human
diseases, including infectious diseases, genetic conditions and cancer. This field of medicine is
rapidly evolving and offers new avenues for targeting “the undruggable”. In this infographic,
we’ll explore why.
Let’s start by asking – what is RNA?
RNA
ribo
ac
{
nucleic
id }
A biological molecule that is similar to DNA,
but has only one helical strand of ribonucleotide bases:
DNA, trapped in a cell’s nucleus, is transcribed
to RNA that can then be translated to produce
proteins within the cytoplasm. Proteins are the
Adenine (A)
functional workhorses of the cell, conducting a
myriad of important biological processes.
Guanine (G)
DNA to RNA
Cytosine (C)
nd export to cytoplasm
and export to cytoplasm
RNA in cytoplasm
Uracil (U)
Protein translation
from mRNA at
DNA in nucleus
at
Protein
Several key discoveries in RNA biology
have paved the way for RNA therapeutics:
1956
1962
1977
1998
Rich and Davies
RNA replicase
RNA splicing
Discovery of RNA
demonstrate that two
is discovered.
is discovered.
interference.
RNAs can form base
pairs
with one another.
1961
1970
1993
Messenger RNA
Reverse transcriptase
(mRNA) is discovered.
is discovered.
Discovery of microRNA.
RNA is a key player in the central dogma of molecular biology. Considering that many human
diseases are caused by errors in this dogma, we can start to appreciate how useful RNA can
be as a therapeutic modality.
RNA therapeutics are likely to change
the standard of care for many diseases.
Targeting the undruggable
Only 0.05%
of the human genome has
been drugged by small molecule drugs and
Fast development
antibodies, as most of the genome does not
RNA therapeutics can be designed and
encode protein. Some RNA molecules can
developed much faster than traditional
target mRNAs and noncoding RNAs directly,
small drugs or gene therapies. The design
meaning that RNA can hypothetically target
and synthesis of RNA molecules is also more
any gene of interest, even if it does not
adaptable, a critical feature for responding
encode a protein.
to public health emergencies.
Stimulating the
Short half-life
immune system
HL
Some RNA molecules, like mRNA, have
RNA can be used to effectively stimulate
a short half-life. This can be beneficial
the immune system, creating new
as it enables a controlled and reversible
opportunities for vaccine development.
therapeutic effect.
The BNT162b2 COVID-19 vaccine was
the first mRNA-based vaccine to be
approved for human use in history.
Low risk of mutagenesis
Unlike gene therapies, RNA therapeutics
Personalized medicine
do not integrate into the genome,
and do not cause unintended mutations.
RNA therapeutics can be customized
for individual patients.
The different types of RNA
Scientists have discovered a variety of RNA molecules that have diverse roles, and many
are still yet to be determined. RNA molecules can be used to modulate gene expression in
various ways, such as by expressing therapeutic proteins, targeting RNA molecules to alter
their function or silencing specific genes, for example.
Examples of RNA therapeutics
1
RNA aptamers
RNA
aptamer
Pegaptanib was the first RNA therapeutic
approved by the US Food and Drug
Administration (FDA) for the treatment
of age-related macular degeneration (AMD).
Pegaptanib interacts with vascular endothelial
growth factor (VEGF), stopping it from interacting
with its receptors.
Protein function
is blocked
2
Antisense oligonucleotides (ASOs)
Anti-sense RNA
to target RNA and modulating gene
expression either by:
• inhibiting translation
• promoting RNA degradation
• or altering splicing.
mRNA therapies work by introducing synthetic
mRNA molecules into cells, which instruct the
cell to produce a specific protein. This protein
could be used to treat a disease or to trigger an
immune response.
mRNA is being used to create flu, RSV and HIV
vaccines, and therapies to treat conditions such as
type I glycogen storage disease.
Nusinersen was approved by the US FDA in 2016
to treat spinal muscular atrophy (SMA), a genetic
neuromuscular condition.
It corrects splicing errors in the SMN2 gene,
increasing production of the functional SMN
protein and improving motor function.
1
3
2
to target RNA and modulating gene
• inhibiting translation
• promoting RNA degradation
• or altering splicing.
mRNA therapies work by introducing synthetic
mRNA molecules into cells, which instruct the
cell to produce a specific protein. This protein
could be used to treat a disease or to trigger an
immune response.
mRNA is being used to create flu, RSV and HIV
vaccines, and therapies to treat conditions such as
type I glycogen storage disease.
Nusinersen was approved by the US FDA in 2016
to treat spinal muscular atrophy (SMA), a genetic
neuromuscular condition.
It corrects splicing errors in the SMN2 gene,
increasing production of the functional SMN
protein and improving motor function.
1
3
2
• inhibiting
translation
• promoting
RNA degradation
Anti-sense RNA complexed
with pre-mRNA or mature mRNA
• or
altering splicing.
Nusinersen was approved by the US FDA in 2016
Spliced mRNA
to treat spinal muscular atrophy (SMA), a genetic
neuromuscular condition.
Modulation of splicing
Degradation
of pre-mRNA
of mature RNA
It corrects splicing errors in the
gene,
SMN2
increasing production of the functional SMN
protein and improving motor function.
3
Double stranded RNA
RNA interference (RNAi)
Dicer
Small interfering RNA
Use small RNA molecules to silence target
genes, halting the prevention of proteins
RISC
by interfering with mRNA.
siRNA and
The two main forms of RNAi are genome
mRNA complex
derived
microRNAs (miRNAs) and small
interfering RNAs (siRNAs).
Currently four siRNA therapeutics are
approved by the FDA.
mRNA degradation
4
mRNA
C
AAA
(including mRNA vaccines, therapeutics and cell therapies)
Mature mRNA
• Introduced into cell
mRNA molecules into cells, which instruct the
cell to produce a specific protein. This protein
could be used to treat a disease or to trigger an
immune response.
mRNA is being used to create flu, RSV and HIV
vaccines, and therapies to treat conditions such as
type I glycogen storage disease.
Nusinersen was approved by the US FDA in 2016
to treat spinal muscular atrophy (SMA), a genetic
neuromuscular condition.
It corrects splicing errors in the SMN2 gene,
increasing production of the functional SMN
protein and improving motor function.
1
3
2
4
• Undergoes translation
cell to produce a specific protein. This protein
could be used to treat a disease or to trigger an
immune response.
mRNA is being used to create flu, RSV and HIV
vaccines, and therapies to treat conditions such as
type I glycogen storage disease.
Nusinersen was approved by the US FDA in 2016
to treat spinal muscular atrophy (SMA), a genetic
neuromuscular condition.
It corrects splicing errors in the SMN2 gene,
increasing production of the functional SMN
protein and improving motor function.
1
3
2
4
cell to produce a specific protein. This protein
could be used to treat a disease or to trigger an
immune response.
mRNA is being used to create flu, RSV and HIV
vaccines, and therapies to treat conditions such as
Functional enzyme
or antigen is produced
type I glycogen storage disease.
To date, the development of RNA therapies has focused largely on ASOs, RNAis and
mRNA-based drugs or vaccines.
RNA theraputic type
118
150
Summary of
RNA therapeutic
100
Number
54
ongoing clinical
44
of
trial landscape.
trials
50
6
Adapted from
Curreri et al.
0
mRNA
siRNA
ASO
Other
Manufacturing RNA therapies
Different methods and bioprocessing workflows are used to design and develop
RNA therapeutics. Here’s a “classic” example of a manufacturing process.
1
Once a workflow has been established, production facilities can
typically “switch gears” quickly and adapt this workflow to produce
Obtain RNA sequence(s)
other types of RNA drugs.
for desired indication.
Often gathered from
a digital bank.
2
3
4
5
DNA template production
Drug substance
Drug product
Fill and finis
manufacturing
formulation
• Clone
• Purificatio
• Cell
-free transcription
• Self
-assebly of RNA
• Expand
• Sterilization
of mRNA
lipid
nanoparticles
• Linearize
• Packaging
7
6
Subject to regulatory
Clinical trials to test
approval, global
efficacy and safety
production and distribution
of the product.
may be the next step.
Despite many RNA
therapeutics entering clinical
trials, only
a few have
received FDA approval.
RNA therapies – the present and the future
Challenges associated with RNA-based therapeutics include:
Instability
Making sure RNA
molecules are stable
and developing effective
delivery methods to
target specific cells
Delivery
without degradation
is a challenge.
Addressing the potential of
RNA molecules to activate
the immune system,
Demonstrating safety
Immunogenicity
which can lead to adverse
and efficacy and gaining
reactions or reduced
regulatory approval
therapeutic efficacy
for RNA therapies
can be a long and
Clinical validation
expensive process.
The swift expansion of RNA therapeutics can be attributed to the resolution of some
of these challenges. Room for improvement remains, however the global RNA therapy
clinical trials market is expected to reach
$3.5 billion
by 2030.
Sponsored by
Sponsored by
Download the Infographic for FREE Now!
Information you provide will be shared with the sponsors for this content. Technology Networks or its sponsors may contact you to offer you content or products based on your interest in this topic. You may opt-out at any time.