10 June 2013

DNA on the conveyor

A method of producing high-quality DNA molecules on an industrial scale has been developed

DailyTechInfo based on Karolinska Institutet: New method of mass-producing high-quality DNA

Recently, more and more scientists are turning their attention to DNA molecules as nodes and components of various drugs, nanodevices, logical elements of biological computers, biological devices for recording and storing information. All these studies are still being conducted within the walls of various laboratories, but when it comes to the introduction of the developed technologies, one big problem will arise. This problem lies in the absence of technological methods for the large-scale production of short DNA chains, oligonucleotides, which are the starting material for the production of longer DNA molecules.

Realizing that the problem of mass production of DNA molecules will sooner or later become very acute, researchers from the Karolinska Institutet, Sweden, and Harvard University have jointly developed a technology suitable for the production of oligonucleotides of certain types in large quantities. This technology, the description of which was published in the journal Nature Methods (Ducani et al., Enzymatic production of 'monoclonal stoichiometric' single-stranded DNA oligonucleotides), can fully satisfy the needs of scientists, researchers and production workers with the main types of raw materials and new methods, without which it is impossible to conduct some studies.

"We used the method of enzymatic production to create a system that not only improves the quality of the produced oligonucleotides, but also allows us to deploy large-scale production of them. To do this, we use certain types of microorganisms that work as "numerical software machines", producing large quantities of short DNA chains, the structure of which is embedded in the genome of these microorganisms. At the same time, the cost of such a method of DNA production is significantly lower than the cost that other methods can provide," says Bjorn Hogberg, a scientist from the Swedish Medical Nanoscience Center, which is a division of the Department of Nanotechnology at the Karolinska Institute.

The process of bio-production of DNA chains, which uses programmed microorganisms, makes it possible to produce molecules of almost any length in large quantities. Unlike the existing methods of artificial DNA synthesis, where the number of errors in molecules increases proportionally to the length of the molecule, the new biosynthesis method allows to obtain oligonucleotides several hundred bases long, containing practically no errors in the genetic code.

The original DNA molecules are produced by microorganisms as one infinite molecule consisting of repeating identical fragments. At the edges of these fragments there are so-called "hairpins" consisting of certain molecules. The molecules of these "hairpins" intensively react with restriction enzymes, which act as molecular biological "scissors" that cut a long DNA molecule in strictly defined places. Using this method, by encoding microorganisms in an appropriate way, it is possible to produce oligonucleotides of several types at once, obtaining a mixture of various short DNA chains with predetermined proportions at the output, which immediately allows using such a mixture as a ready-made drug.

"Medicines based on oligonucleotides, short DNA chains, already exist and are available to people in extremely limited quantities at an incredibly high price. Our method of producing oligonucleotides will allow us to produce large quantities of similar drugs, cleaner, more effective and at a significantly lower cost," concluded Dr. Bjorn Hegberg.

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