Oligonucleotides, the language of life in small doses

A technological revolution can start with a key concept, the application of an equation or, often, with the development of a particular material. Steels, alloys, concretes, liquid fuels, semiconductors or polymers are examples that changed the history of mankind and today are ubiquitous in our lives.

The pharmaceutical industry is no different. Thus, the ability to elucidate the structure of organic molecules and the development of their chemical synthesis or the production by fermentation of drugs such as penicillin in the 19th and 20th centuries were giant steps that made drugs universally available.

Since then, the paradigm in the discovery of new drugs and their production has been evolving, progressively moving towards a rational application of our knowledge of cell mechanisms, searching for new treatments as opposed to the more classical processes where chance often plays an important role.

On the road to the rational design of drugs, the material that holds and encodes the information that defines these mechanisms shines with its own light: nucleic acids. Among them, the well-known DNA molecule, a long chain that stores all the information necessary for the functioning of our cells. However, on a practical level, and as a laboratory tool or as a basis for the manufacture of drugs, interest is usually focused more on smaller nucleic acids, artificially created and with structures derived from or related to DNA, which biologists call oligonucleotides.

But let’s go with a bit of history by marking the beginning in 1953. In that year, after a stormy academic relationship concerning the work of the researcher Rosalind Elsie Franklin, Watson and Crick determined the precise structure of the DNA double helix. A year later, Severo Ochoa and, in ’56, Arthur Kornberg discovered how the information contained in this DNA is copied and transcribed into another smaller molecule, messenger RNA, allowing the transmission of information and orders to the cellular machinery. They were followed by a significant number of scientists with notable contributions in this field, where there is no lack of the traditional controversy over exclusions from the Nobel prizes.

Special mention should be made of the Indian molecular biologist Gobind Khorana, who, after an enormous amount of work and thanks to oligonucleotides, decoded the complete code by which the cell transforms the information in its DNA into proteins, and the Frenchmen François Jacob and Jacques L. Monod, who specified the complex regulatory mechanisms of this biomolecular microcosm. Once the Rosetta Stone of biology had been deciphered, we could now understand, manipulate and communicate with cells. This opened up a whole world of applications.

In 1973 Stanley Cohen and Herbert Boyer succeeded in incorporating a specific gene into a bacterium. The latter, together with the entrepreneur Robert A. Swanson, founded the now multinational Genentech, inaugurating genetic engineering and the modern biotechnology industry in unison. In the late 1970s and 1980s, tools began to be developed to identify the sequence of any biological sample, including PCR. As early as 2003, the Human Genome Project was completed, completing a total sequence of our genetic code.

Since then, the genetic data available on all types of living beings has increased exponentially, enabling medical advances such as RNA vaccines, which are effective and developed in record time. Based on these data, drugs are being researched and marketed that require DNA editing in cells, identifying specific RNA sequences or triggering cellular mechanisms in their development, production or operation. These are technologies labeled with acronyms, unintelligible to the general public (RNAi, aptamers, antisense, CRISPR, etc.), but which require lower initial investments before starting clinical trials and which target specific cellular mechanisms, which is very interesting for making treatments for rare diseases profitable. In these technologies, oligonucleotides are as basic as microchips in electronics. They communicate or interfere with biological processes, balance concentrations of pathogenic proteins, are capable of binding to all kinds of molecules and allow us to give precise instructions to our cells. In laboratories, their shapes are designed, analyzed and modeled, predicting their behavior with powerful software and experimental techniques of controlled selection.

The pharmaceutical industry related to oligonucleotides pivots on a complex universe of patents and industrial secrets, while startups and specialized companies proliferate in the United States, Europe and Asia, always under the watchful eye of big pharmas in search of new opportunities. All this also boosts auxiliary industries, necessary for producing raw materials, releasing nanotechnology drugs or developing new production and scaling-up processes. And, like any high-tech area, it requires solid value chains to avoid stock-outs, technological gaps and imbalances in the balance of payments.

We are facing a silent technological revolution where business initiatives aimed at not missing windows of opportunity are essential for a country. This is the case of the research and industrial development project Oligofastx (www.oligofastx.com), carried out by seven Spanish companies specialized in oligonucleotides, and which addresses all these challenges from a 360-degree perspective. The project has received funding from the Center for Industrial Development and Innovation (CDTI) under the Science and Innovation Missions program.

Juan Manuel Báez
Project Coordination Department/Pharma Mar, S.A. Master in Business Administration by CEF.

Source: https://acef.cef.es/oligonucleotidos-lenguaje-vida-pequenas-dosis.html