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The OLIGOFASTX team is focused on the development of oligonucleotide-based therapies for certain rare diseases covering the whole cycle: from research to manufacturing and distribution of future new oligonucleotide-based drugs. To this end, the companies that make up the consortium are specialised in one area, which in combination provides a form of collaboration that allows for highly innovative results.
The different areas of work include the identification of new therapeutic targets and biomarkers, new targeted delivery systems to reach target tissues more efficiently and the development of new innovative strategies for more sustainable oligonucleotide synthesis. And within this whole cycle, there is a group of molecules that are key to the synthesis of oligonucleotides: enzymes.
Enzymes are a fundamental tool in the advancement of oligonucleotide therapy. Thanks to their ability to catalyse specific reactions, enzymes enable the synthesis and modification of oligonucleotides with greater efficiency and precision. In this article, we explore how enzymes are driving the development and application of oligonucleotides in medicine.
Introduction to enzymes and their role in oligonucleotide processing
Enzymes are molecules that speed up chemical reactions in our body and are essential for the proper functioning of the metabolism. In the medical field, enzymes also play a crucial role in the treatment of oligonucleotides, which are small nucleic acid molecules used to treat genetic diseases, viral infections and cancer.
Enzymes are necessary for the activation and degradation of oligonucleotides in the body, allowing them to reach their therapeutic target. In addition, enzymes can also improve the efficacy and safety of oligonucleotides by helping to reduce toxicity and increase bioavailability. As a result, research in the field of enzymes and oligonucleotides is constantly evolving, leading to new discoveries and more effective treatments for a wide variety of diseases.
Enzymes in oligonucleotide biosynthesis
Biosynthesis of oligonucleotides occurs naturally in the cells of living organisms through the process of transcription. An RNA molecule is synthesised from a strand of DNA. The transcription process is catalysed by RNA polymerases. Without this enzyme, the process would never take place. In eukaryotes there are 3 types of RNA polymerases, each specialising in a different type of RNA: RNA polymerase I for ribosomal RNA, RNA polymerase II for messenger RNA and snRNA, and RNA polymerase III for transfer RNA.
In general, the architecture of bacterial and eukaryotic polymerases is very similar, although eukaryotic polymerases have more subunits. In both cases it is structurally very well organised. DNA passes through the RNA polymerase structure through two gaps. The nucleotides enter through a different hole and are incorporated into the active centre. Inside the enzyme is a small transcription bubble of fixed size that moves as the polymerase proceeds.
This process is postulated as a new technique for the industrial in vitro synthesis of oligonucleotides, more sustainable, with greater selectivity and lower cost, and is therefore one of the cornerstones of the Spanish OLIGOFASTX consortium. Our vision is to create a platform that facilitates and contributes to the generation in Spain of a biopharmaceutical industrial fabric specialised in the development sustainable oligonucleotide-based therapies.
Specific enzymes used in the chemical synthesis of oligonucleotides
On the other hand, enzymes are also widely used in numerous in vitro synthesis reactions due to their high catalytic capacity. Enzymes are also involved in the process of oligonucleotide synthesis, which is mainly based on the formation of internucleosidic phosphodiester bonds.
In the OLIGOFASTX project, enzyme engineering is carried out to optimise in vitro transcription reactions that improve oligonucleotide synthesis using these enzymes.
Enzyme production
Although enzymes occur naturally in living organisms, biotechnology makes it possible to produce and use them industrially for the benefit of society. In the OLGIFOASTX consortium, we have GMP-approved partners for the production of all types of proteins – including enzymes – for preclinical experiments, clinical trials and commercialisation.
Recent improvements thanks to the use of new enzymes and advanced techniques
Enzymes are the key to the constant advancement of oligonucleotide therapy, and thanks to new advanced techniques, significant improvements in the field of medicine have been achieved.
The use of highly specific and efficient enzymes has enabled the creation of more precise and effective oligonucleotides, resulting in greater success in the treatment of genetic and chronic diseases.
Future perspectives on how enzymes can further improve oligonucleotide therapy
One of the most interesting future prospects is the use of enzymes to improve the delivery of oligonucleotides to different tissues and organs. In addition, new enzymes are being investigated that may improve the stability and duration of oligonucleotides in the human body, which could reduce the frequency of administration and improve the efficacy of treatment.
Enzymes are also being developed that can help remove the oligonucleotides from the body more effectively, which would reduce side effects and increase the safety of the treatment.
Other enzymes would be used to produce already modified oligonucleotides that can be used in disease therapies.
In essence…
In conclusion, enzymes play a crucial role in the steady progress of oligonucleotide therapy. These biological molecules act as catalysts to accelerate the chemical reactions necessary for the synthesis and degradation of oligonucleotides. Thanks to enzymes, scientists can design more complex and specific oligonucleotides, which has led to greater efficacy in the treatment of genetic and viral diseases.
At OLIGOFASTX we research and work with enzymes, a key component in improving the quality of life of patients affected by rare diseases.
Sources:
- Spanish Society of Biochemistry and Molecular Biology: https://sebbm.es/
- Spanish Association of Biocompanies: https://www.asebio.com/
- Journal of Pharmacy and Research: https://www.elsevier.es/es-revista-revista-farmacia-investigacion-141
- Confederation of Pharmacy Business of Spain: https://www.cefe.es/
- American Society for Biochemistry and Molecular Biology: https://www.asbmb.org/
- Biochemical Society: https://www.biochemistry.org/
- Journal of Medicinal Chemistry: https://pubs.acs.org/journal/jmcmar
- Image 1: https://www.the-scientist.com/features/protein-synthesis-enzymes-have-evolved-additional-jobs-67549
- Image 2: https://www.genengnews.com/topics/worlds-longest-oligo-produced-using-de-novo-synthesis/