A new process that could lead to stickier and better gene therapy drugs has been developed by the researchers at Michigan Technological University. The drugs, called antisense DNA, are made from short, single strands of synthetic DNA. They work by blocking cells from making harmful proteins, which can cause maladies ranging from cancer to Ebola to HIV-AIDS. Only a couple of these synthetic DNA drugs are on the market, but a number are in clinical trials, including a potential treatment for ALS (lat. amyotrophic lateralibus lumbos). Disease organisms can inject harmful proteins into our bodies, and so can mutations in our own genetic material.
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. Drugs made from synthetic DNA are tailored to grab onto these mutant messenger RNA molecules, binding to them and preventing them from churning out toxic proteins. However, a serious shortfall with synthetic DNA is that it can be wimpy. Sometimes it loosens its grip, setting the messenger RNA free to resume its dirty work.
Scientists know how to make synthetic DNA stickier One way is to tack on some functional groups of atoms with a partial positive charge, called electrophiles. The electrophiles react with nucleophiles - groups in the RNA with a partial negative charge. This forms a powerful covalent bond, locking the RNA up for good. Unfortunately, the conventional process for making synthetic DNA involves a final bath in ammonia. The ammonia washes away the chemical groups used to assemble synthetic DNA, called linkers and protecting groups - and it also neutralizes electrophiles. And other processes are expensive, unreliable and can involve toxic materials.
In synthesizing DNA, the group uses different chemicals to make linkers and protecting groups. These chemicals wash away easily in a relatively harmless solution that doesn't destroy electrophiles. The new process has other advantages: it's cheap and safe, making it ideal for manufacturing life-saving drugs. Plus, it gives a new tool to microbiologists and biochemists, who could use the technique to develop synthetic DNA with a whole array of new properties.