Antisense Drugs

By: Trang Nguyen

A new technology has the potential to revolutionize the way we treat diseases. This technology, called antisense drug therapy, works to prevent diseases at the genetic level. However, before delving into the details of antisense drug therapy, it is critical to review the

The process of protein synthesis begins from a double stranded DNA molecule, which contains the gene that codes for the specific protein. DNA is then transcribed into single stranded mRNA. The mRNA is then “read” through a ribosome, and amino acids are assembled to synthesize the specific protein. It is important to note that this mechanism only functions with single stranded mRNA.

Many diseases are caused by genetic mutations, which lead to improperly folded proteins.Antisense drugs, also called antisense oligonucleotides, work by targeting these disease-causinggenes. This is done by engineering a short, single strand of nucleic acid that will bind to themRNA strand of the gene of interest, creating a double stranded region. Doing so effectivelyprevents the faulty protein from being produced, because mRNA can only be processed if it is single stranded.

Think of it as a printer. Instead of single sheets of paper being fed into the machine, it is one continuous sheet of paper. This continuous sheet of paper represents the single stranded mRNA. The printed product can be thought of as the assembled, disease-causing protein. Now, the printer can only process the paper if it is a single layer of paper, much like the single stranded mRNA. An antisense drug would work by essentially binding another layer of paper onto the original sheet, rendering it unreadable by the printer. This prevents the production of the disease-causing protein.

Antisense drugs have many potential benefits, and are currently being researched to treat diseases such as lung cancer, pancreatic carcinoma, diabetes and arthritis. One of the most promising aspects of antisense medication is their ability to act more selectively than conventional drugs, which can consequently cause less negative side effects. Additionally, antisense medications are relatively inexpensive in comparison to conventional drugs. There is also hope for the ability to target a broader range of diseases because of the flexibility of designing the antisense drugs.

Despite these benefits, however, there are still several downsides that must be addressed. One problem that researchers are running into is the body’s natural response to foreign substances, resulting in many of the antisense drugs being rejected or destroyed within the cell. Additionally, it is difficult to predict the short and long term side effects of using gene directed medications.

Antisense drug therapy is still a developing technology, but significant progress has been made in the field. One of the companies that is on the forefront of antisense medication is Isis Pharmaceuticals. In January 2013, the Federal Drug Administration approved the distribution of one of their first antisense drugs, Kynamro. This drug targets the gene for the rare genetic disease, homozygous familial hypercholesterolemia, which can drastically increase the risk of early heart attacks. Although this drug will not benefit as many people as an anti-cancer drug may, this is a tremendous hope for antisense research as it gains recognition in the scientific community.