The NHS recently approved a new cholesterol-lowering injection that will be available to 300,000 people in the next three years.
The drug-inclisiran-will be injected twice a year. It is mainly used for patients with genetic diseases that cause high cholesterol, patients who have already suffered from heart disease or stroke, or patients who do not respond well to other cholesterol-lowering drugs (such as statins).
There is a lot of excitement surrounding the approval of the drug, both because it may be possible, and because the drug uses a technique called “gene silencing.” This is an emerging treatment technique that works by targeting the root cause of the disease rather than the symptoms it causes. It does this by targeting specific genes and preventing it from making the proteins it produces.
So far, most therapies using gene silencing technology have been used to treat rare genetic diseases. This means that cholesterol jabs will be one of the first gene-silencing drugs used in the wider treatment of humans. Researchers are currently studying whether gene silencing can be used to treat a variety of health conditions, including Alzheimer’s disease and cancer.
Gene silencing drugs work by targeting specific types of RNA (ribonucleic acid) in the body, called “messenger” RNA. RNA exists in every cell of the body and plays an important role in the flow of genetic information. But messenger RNA (mRNA) is one of the most important types of RNA that our body has, because it copies and carries genetic instructions from our DNA, and makes specific proteins according to the instructions.
In the case of cholesterol injection, the effect of gene silencing is to target and degrade a protein called PCSK9. This protein is involved in the regulation of cholesterol in our body, but it appears in excess in people with high levels of LDL cholesterol (“bad” cholesterol). Preventing the production of this protein in the first place will lower cholesterol levels.
In order to target this specific mRNA, researchers need to create another type of RNA in the laboratory—a synthetic version called small interfering RNA (siRNA). This is a highly specific RNA that can be used to target specific mRNA. In this case, siRNA specifically targets mRNA carrying PCSK9 protein instructions. It binds to its target mRNA and destroys instructions, thereby significantly reducing the amount of these proteins produced.
Gene therapy usually uses viral vectors for delivery-a virus-like vector that can deliver genes to our cells like a virus infects cells. So far, viral vector therapy has been used to treat rare hereditary blood diseases, hereditary blindness, and spinal muscular atrophy.
Although viral vectors are very effective for one treatment, due to a poor immune response, it may not be possible to provide a second dose when needed. These drugs are also extremely expensive.
Therefore, many gene silencing drugs currently under study are delivered using different technologies. These drugs, called non-viral vector gene therapy, use nanoparticles to deliver drugs, which protect the drug from degradation in the blood, so it can be specifically delivered to a target, such as the liver, which is the target of cholesterol injection.
Gene silencing therapies provided by non-viral vectors seem to be more promising because they can be administered multiple times and have limited side effects. Currently, non-viral vector therapy is used to treat a rare genetic disease called hereditary transthyretin-mediated amyloidosis, as well as mRNA vaccines such as BionTech/Pfizer and Moderna.
However, it is interesting that the cholesterol jab is not buried in the nanoparticle, nor is it transmitted through the viral vector. Instead, siRNA has been extensively modified in the laboratory to withstand degradation in the blood. It also has a ligand (a kind of sugar molecule that resembles a hook) that allows it to specifically target liver cells.
More gene-silencing drugs are currently being studied to treat various other diseases, including kidney (for example, to prevent adverse reactions after transplantation), skin (scarring), cancer (including melanoma, prostate, pancreas, brain and other diseases). Tumors) and eye diseases (such as age-related macular degeneration and glaucoma). Researchers are also studying whether gene silencing therapy can be used to treat neurological and brain diseases, such as Huntington’s disease and Alzheimer’s disease.
Each of these gene silencing therapies will use technology similar to other drugs that currently exist-by targeting specific genes or proteins and turning them off. But in the case of cancer, because it is very complex, it may need to target many different proteins.
These gene silencing technologies need to be proven effective in further clinical trials before they can be widely used. Another important challenge is to ensure that the cost of these drugs is kept low so that many people can get them. But in general, these developments are very promising: gene silencing drugs are more specialized because they can target specific proteins in our cells. This may be why they are more successful in treating diseases than current treatment methods.