Oligonucleotides (commonly referred to as oligos),
are short single stranded DNA or RNA molecules, typically containing 15-20
nucleotide residues. In the modern biopharmaceuticals and biotechnology, the
applications of these molecules are vast, including (but not limited to)
genetic testing, fundamental biomolecular research, and forensic analysis.
Presently, researchers are actively exploring the applications of
oligonucleotides as pharmacological interventions for the treatment of various
diseases (especially cancer, genetic disease and rare diseases). There are two
principle approaches used for the development of RNA-based drugs; double
stranded RNA-mediated interference (RNAi) and antisense
oligonucleotides (ASO). Both approaches are currently in clinical trials
for targeting of RNAs involved in various diseases, such as cancer and
neurodegeneration.
§ RNA
Interference Therapeutics
RNAi is a natural
process of post-transcriptional gene silencing, involving short strands of
nucleic acids. Cells use this process to silence and / or inhibit gene
expression, via the targeted degradation of specific (unwanted) mRNA
molecules. From an application perspective, the gene specificity of RNAi is the
primary reason why it is being considered for therapy development. In theory,
RNAi based therapeutics are capable of treating indications, such as
age-related macular degeneration (AMD), hepatitis C and various forms of cancer,
which are generally perceived as hard to treat with conventional
pharmacological options. The basic mechanism of RNAi is
a three step process of gene silencing.
§ Antisense
Oligonucleotide Therapeutics
Antisense
oligonucleotides (also known as ASOs) are short RNA / DNA based structures
whose sequence specifically binds to the target RNA and inhibits the gene
expression. They have a sequence that is complementary to a sequence within a
specific mRNA. Antisense therapeutics are considered to be one of the most
promising agents for impairing the protein production and blocking the function
of the specific target gene of interest in the human genome. Presently, this
process forms the basis for many therapeutics being investigated in different
stages of clinical trials for treatment of a range of cancers, viral diseases,
and genetic disorders. Antisense oligonucleotides are designed to target the
mRNA using a number of different mechanisms.
With the success of the first antisense
oligonucleotide, fomivirsen, approved in 1998 for the treatment of disease cytomegalovirus
(CMV) retinitis, the field of antisense oligonucleotide therapeutics has
evolved rapidly with multiple approved / late stage clinical candidates and a
long preclinical pipeline. With the ability to interfere with the process of
gene expression, antisense oligonucleotides are considered to be one of the
best options for gene manipulation and impairment of protein production. These
therapeutic interventions have shown to have potential to treat a variety of
disorders, including oncological
disorders, genetic diseases, hepatic diseases, respiratory disorders and
infectious diseases.
Amongst the recent developments, important to mention that
certain companies are evaluating the therapeutic efficacy of antisense RNA (which
are different from the conventional antisense DNA). These antisense RNAs
read in the opposite direction of the coding strand and bind to the coding
strand of mRNAs and further, prevent them from being expressed. In fact,
oligonucleotide drug developers have also begun investigating the relevance of
these interventions against the novel Coronavirus (COVID-19). We believe that a
breakthrough in this disease area is likely to provide a significant impetus.
Given the pace of innovation and developments in this upcoming market, we can
expect antisense
oligonucleotides to become a major therapeutic modality in the foreseen
future.
For more information, please click on the following:
https://www.rootsanalysis.com/reports/antisense-oligonucleotide-therapeutics-market.html