New Process for Creating Synthetic DNA Drugs Can Ultimately Save Lives

Scientists at Michigan Technological University have created a process for creating DNA that prevents cells from forming harmful proteins that result in a number of maladies; this process can lead to the development of more effective gene therapy drugs. The article on this work was published in Organic Letters in July.

The synthetic DNA drug, called antisense DNA, is designed to block cells from creating proteins that are harmful to the body and can result in illnesses ranging from HIV to Ebola to cancer. Thus far, the number of synthetic DNA drugs that are available on the market is very limited (only a couple), according to the Michigan Tech press release. However, a number of these kinds of drugs have reached clinical trials, including one that could potentially be used as treatment for Amyotrophic Lateral Sclerosis (ALS), more commonly known as Lou Gehrig’s disease.

Mutations that occur within our own genetic material as well as disease organisms both create harmful proteins within the body that can lead to the aforementioned diseases.

According to the press release, “When all goes well, messenger RNA molecules in our cells produce the good proteins that are essential to life. However, when mutations occur, messenger RNA can go rogue and start making proteins that make us sick.”

Synthetic DNA drugs are designed to adhere to the “mutant” molecules of messenger RNA and by binding to them, they are then able prevent them from creating harmful proteins. However, the level of adherence that the synthetic DNA are capable of is not always strong; if it loosens its grip on the messenger RNA, the RNA are then free to resume the production of toxic proteins.

Shiyue Fang, PhD, professor of chemistry at Michigan Technological University and coauthor of the article, said, that as a way to remedy the drawbacks of the synthetic DNA drugs, scientists have now found a way to make the DNA “stickier.” One way to successfully do this is to add electrophiles, groups of atoms with a partial positive charge, to the synthetic DNA. According to the press release, the electrophiles will react with nucleophiles, groups of atoms in the messenger RNA that hold a partial negative charge. Through this reaction, a covalent bond is formed that is strong enough to effectively bind the potentially harmful RNA messengers.

Current conventional processes that are used to create synthetic DNA involve a “final bath in ammonia,” according to the press release. The big drawback to this is that the “linkers” and “protecting groups” that are used to create synthetic DNA are washed away by the ammonia. In addition, ammonia neutralizes the electrophiles, and for a powerful covalent bond to be formed, the electrophiles need to retain their partial positive charge.

Dr. Fang said, “So far, it’s been very difficult to incorporate electrophiles in synthetic DNA. It’s been like treating a garden with an herbicide that kills everything. [That’s about to change.] Our method just takes out the weeds.”

The researchers used different chemicals to create the “linkers” and “protecting groups” when they synthesize DNA. These new chemicals are placed in a “relatively harmless” solution that can easily wash away the chemicals. More importantly, the electrophiles remain charged and intact.

This process created by Dr. Fang and his team can be used by microbiologists and biochemists as a tool to create synthetic DNA with all different properties, according to the press release. Furthermore, they state that the process is both safe and cost effective, which allows for the creation of better gene therapy drugs that can be used to save a number of lives.