Oligonucleotide therapeutics represent a cutting-edge approach in the field of medicine, offering new avenues for the treatment of a wide range of diseases. They are comprised of short stretches of synthetically made DNA or RNA bases (~20 bases ) designed to specifically target and modulate gene expression.
We specialize in providing comprehensive oligonucleotide services that span the entire discovery and development process for oligonucleotide therapeutics including design, synthesis, screening for potency and safety, off target effects, mechanism of action or proof of concept studies relevant to the disease biology, DMPK, tolerability and early safety, and GLP studies to support filing for First in Human.
How can short pieces of DNA or RNA work as drugs?
Unlike Gene Therapy, oligonucleotide drugs targeting RNA, such as small interfering RNA (siRNA) and antisense oligonucleotides (ASOs) have a transient effect in the body, and do not permanently modify the patients genome. Sequence-based targeting of RNA, uses synthetically produced, matching stretches of oligonucleotides to bind with exquisite precision to a specific RNA target, causing subsequent changes in protein expression, either by altering splicing of the immature RNA or causing rapid turnover of that RNA before a protein can be made.
The technology is rapidly expanding, and oligonucleotides can also have more diverse mechanisms of action, including binding protein targets with antibody-like affinity (Aptamers), steric hindrance of RNA structures and RNA binding proteins, modulating splice variants, editing RNA and upregulating protein expression.
This enables targeting of proteins or RNA that are implicated in various disease processes, including monogenetic disorders, progressive metabolic or neurodegenerative disease, cancers, and viral infections. This precision targeting makes oligonucleotide drugs a promising alternative to traditional small molecule drugs and biologics.
Going Where Smaller Molecules Have Failed
One of the key advantages of oligonucleotide therapeutics is their ability to address previously "undruggable" targets. Traditional drugs often struggle to interact with certain proteins or genetic sequences due to their complex structures or locations within the cell. Oligonucleotides, however, can be designed to bind with high specificity to these challenging targets, opening up new possibilities for treatment. Initially hampered by their large size and limited biodistribution, advancements in delivery technologies have improved the stability and bioavailability of oligonucleotide drugs, making them more effective in reaching their intended sites of action within the body.
While the oligonucleotide field has been around for over two decades, it has gained significant clinical success in the past six years, with 21 drugs already on the market for various indications, and hundreds more approved for use in human trials. This success is expected to accelerate as the field gains momentum.
Evotec Oligonucleotide Services
Discovery Expertise
From early stage research, a target idea or an understanding of disease biology, our team of disease experts can help with assay development or target validation. This deep therapeutic area or mechanistic expertise and access to patient molecular databases can be harnessed through all stages of the project to help initiate or progress your research and provide proof of concept studies for oligonucleotide drug discovery.
We have an expert design team for the design of oligonucleotide libraries or Lead Optimization, complemented by small to large scale oligonucleotide production facilities across 2 sites in Europe including linker and conjugation expertise. Our cutting-edge screening technologies, deep disease and modality experience, enable state of the art tailor made screening solutions to identify the most potent and safe oligonucleotide candidates for progression.
With a focus on mechanistic studies and strong disease area expertise, in various therapeutic areas, including oncology, metabolic diseases, CNS diseases, rare diseases, infectious disease, and women's health. We are able to provide the most appropriate screening system for each therapeutic area in both in vitro and in vivo systems that are both modality and disease appropriate.
Development Expertise
Encompassing all critical stages of drug making, our capabilities continue past early stage discovery to everything needed to progress your candidate to First in Human.
From drug metabolism and pharmacokinetics (DMPK) studies, GLP bioanalytical capabilities and IND-enabling tox studies, we ensure that your oligonucleotide therapeutics are optimized for safety and efficacy. We provide support from concept to clinical trials, with the expertise and resources needed to bring innovative oligonucleotide therapies to patients.
By understanding the unique challenges of each project, our multidisciplinary team develops tailored solutions that meet each project’s specific needs. Evotec can help navigate the complexities of oligonucleotide therapeutics at any stage whether it be early discovery, lead optimization or advancement towards clinical development.
