Many diseases are caused by certain genes being expressed in a dysregulated, or inappropriate, manner. By selectively inhibiting the expression of specific disease-relevant genes, we can potentially treat a variety of diseases, including some conditions which have been considered untreatable until recently. This can be achieved using siRNA therapeutics, which belong to a larger class known as oligonucleotide therapeutics. These artificial (usually synthetic) small dsRNA molecules are designed to harness the natural RNAi pathway to specifically (in a sequence-dependent manner) inhibit the expression of virtually any gene of interest. The focus of biotech and pharmaceutical companies on siRNA therapeutics is continuously increasing as this novel class of drugs is considered one of the most rapidly advancing frontiers in modern drug development.
The following features contribute to the unique advantages of siRNA as a therapeutic class compared to other target inhibitory therapeutic modalities, such as small molecules or antibodies:
Harnessing Natural Pathways
siRNA drugs can be rationally designed to fit into the body’s natural regulatory pathway, making these therapies highly selective – affecting only the target disease-causing gene without affecting other biological processes. The possibility of rational design has the added benefit of shortening the process of selecting drug candidates.
Targeting Proteins Before They Are Produced
Antibodies and small molecules, acting at the level of proteins, require their target proteins to have specific features. Therefore, they are not applicable to all target proteins. In contrast, siRNA therapeutics, acting at the RNA level, are independent of specific protein features, and can be rationally designed for any target. Furthermore, unlike antibodies and small molecules, siRNA therapies can be used to reduce the amount of pathological proteins being produced in the first place.
Affecting RNA Targets, Not Just Proteins
Some diseases are not caused by abnormal proteins, but rather by abnormal RNAs which may belong either to the protein coding RNA class or to the non-protein coding RNA classes. Unlike small molecules and antibodies which can only target proteins, siRNA drugs can also target abnormal RNAs and thus treat pathologies stemming from such malfunctioning RNAs.
Using currently-available technologies, the therapeutic effect of a single administration of an siRNA drug can last up to 6 months, which is impossible with antibodies and especially with small molecules.
Favorable Safety Profile
The safety profile of siRNA compounds is better than that of small molecules, antibodies, and even other classes of oligonucleotide therapeutics (e.g. antisense oligonucleotides) due to their specific design features which help to avoid off-target effects.