New Method of Producing Oligonucleotides Discovered: Bioproduction of Single-Stranded DNA Molecules

Scientists may have taken a giant leap forward when it comes to genetic and molecular biological research. They've developed a new method of manufacturing short, single-stranded DNA molecules called oligonucleotides that could solve many of the problems associated with current production methods.

Oligonucleotides actually constitute a basic tool for researchers. In fact, they play a key part in many fields of science. They can be of value to both DNA nanotechnology and the development of drugs consisting of DNA fragments. In addition, they can give researchers the ability to quickly scan an organism's genome.

In order to actually accomplish the feat of manufacturing oligonucleotides, researchers used bacteria. The process of using bacteria to copy DNA sequences is called bioproduction, and enables the manufacture of large amounts of DNA copies at a low cost. Unlike current methods of synthesizing oligonucleotides, where the number of errors increases with the length of the sequence, this new method also works well for long oligonucleotides of several hundred nitrogenous bases.

"We've used enzymatic production methods to create a system that not only improves the quality of the manufactured oligonucleotides, but that also makes it possible to scale up production using bacteria in order to produce large amounts of DNA copies cheaply," said co-developer Bjorn Hogberg in a news release.

The DNA molecules are first formed as a long string of single-stranded DNA in which the sequence of interest is repeated several times. The long strand forms tiny regions called hairpins, where the strand folds back on itself. These hairpins can then be cut up by the enzymes, which serve as a molecular-biological pair of scissors that cuts the DNA at selected sites. Several different oligonucleotides can then be produced at the same time in a perfectly balanced combination. This is extremely important if they're to be crystalized or used therapeutically.

"Oligonucleotide-based drugs are already available, and it's very possible that our method could be used to produce purer and cheaper versions of these drugs," said Hogberg in a news release.

The findings are published in the journal Nature Methods.