Antisense therapy is a form of treatment for diseases, where a single protein is known to be a major cause of the condition. Antisense medications are targeted to suppress the production of these pathogenic proteins, which are produced in the cell (Figure 2). Antisense molecules are synthesized to bind specifically to the messenger RNA (mRNA) responsible for translating the pathogenic protein at the ribosome (Figure 3). As a result, the production of the protein stops (Figure 3).
Figure 2. Protein production in a cell
The information for producing a protein is contained in the DNA in the cell nucleus. A copy of this information is exported from the nucleus in the form of mRNA. In the cytoplasm (cell interior), ribosomes (factories for protein production) use the mRNA as a blueprint to produce a new, functional protein.
Figure 3. Inhibition of protein production by antisense molecules
Antisense molecules specifically attach to a selected section of mRNA, thereby stopping the process of protein production. mRNA is a single stranded molecule, which ribosomes use as a blueprint for protein production. The single strand is called ‘sense’, because its translation results in a gene product (protein). When mRNA forms a duplex stranded molecule with antisense DNA, this translation is blocked, since the ribosome cannot gain access to the ‘sense’ mRNA.
mRNA sense strand can be read only in this direction by the ribosome.
Antisense strand, which is complementary to the mRNA of the target molecule, blocks the reading of the sense strand.
Antisense medications are, therefore, a new method of targeted therapy to suppress the production of disease-causing proteins, and are currently being investigated to treat various types of cancer, including brain, pancreatic, skin, colorectal and lung cancer.
The application of antisense medication is a promising approach to the treatment of conditions where standard therapies are unsatisfactory. The antisense drug trabedersen
(AP 12009), directed against TGF-β2, has already shown considerable clinical benefit in the treatment of high-grade glioma and is currently in a Phase III study. In addition to that study a Phase I/II study is ongoing in patients with pancreatic cancer, malignant melanoma (skin cancer) and colorectal carcinoma.