The project
DARTER
At DARTER COST Action, we use networking and capacity building to allow RNA-targeting nucleic acid drugs to reach their full potential and become a mainstream therapeutic option.
By involving academics and industry, we aim to assess the state of the art of the delivery of Antisense Oligonucleotides (ASOs) (read more in the sections below) and identify gaps in the knowledge to prioritize and align research efforts. Since 2018, we are developing Standard Operating Procedures for the use of models and methods to assess the delivery of ASOs, as well as to improve comparison and reproducibility between the groups involved in DARTER. This way, we are achieving consensus to allow prioritization of chemical modifications and delivery compounds into preclinical and clinical studies.
We also share unpublished results, particularly negative results, to avoid duplication of efforts and improve focus on effective compounds. The DARTER Action will end in October 2022.
If you want to know more, visit the Memorandum of Understanding (MoU) or the COST web page.
The science
ASOs
Antisense oligonucleotides (ASOs) are a new class of drugs that, through precise targeting in RNA strands, could correct genetic defects for rare inherited diseases, modulate autoimmune or neurodegenerative diseases or target tumours or viruses.
They usually act through binding to specific sequences in coding RNA, so they are highly accurate. They can modulate the function of the target RNA and can be manufactured at a large scale in a standardised manner. Also, unlike other genetic therapies, they do not need to be incorporated into genomic DNA through a viral vector.
There are different types of ASOs, defined by their chemical structure:
- 20 O-methyl phosphorothioate oligonucleotides (2OMe)
- Locked nucleic acids (LNAs)
- Phosphorodiamidate morpholino oligomers (PMO)
- Peptide nucleic acids (PNAs)
They can be bound with other compounds (moieties) to increase their delivery, such as cell-penetrating peptides (CPPs).
ASO therapy development is a dynamic and active field. To date, four ASOs compounds have received a marketing authorisation and there are currently more than 100 clinical trials with antisense compounds.
The main hurdle for their efficacy is their deficient delivery to target tissues but, while translational research on ASO is surging, very little is known about the mechanisms by which ASOs are taken up by different tissues and specific cell. Furthermore, due to the body’s tissue barriers, the circulation of ASOs is restricted, and most of them are not able to reach the central nervous system after injection.
The tools
Networking tools
At DARTER, we organise Training Schools, Short Term Scientific Missions and meetings whose primary goal is to create the scientific network and to empower young researchers. The networking tools supported by COST facilitate sharing the expertise, gaining new knowledge and experience and conducting international multiple laboratory research.
We use the following COST networking tools:
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Working Group Meetings,
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MC & Core Group Meetings,
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Workshops and conferences,
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Training schools,
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Webinars,
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Short Term Scientific Missions (STMS),
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ITC Conference Grants (to increase visibility of young researchers from ITC countries and enable their attendance to high profile S&T conference),
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Data dissemination through various media (research papers, social media, webinars etc.)
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Virtual Mobility Grants
The framework
COST
A COST action is a network of researchers with nationally funded research working together to achieve the objectives & deliverables of Moratorium of Understanding (MoU) and create impact (dissemination & exploitation of results) for no more than four years. The representatives can come from each COST Member participating in the Action. COST Actions may also include representatives from non-COST Countries (i.e. USA, Canada and China) called MC Observers.
COST actions aim at enabling breakthrough scientific developments leading to new concepts and products and thereby contributing to strengthening Europe’s research and innovation capacities.
COST, founded in 1971, is the oldest and widest European intergovernmental framework for trans-European Cooperation in Science and Technology. COST Actions are held for four years. Each action is coordinated, implemented, managed and supervised by the action MC Committee. Each Action MC member represents the COST Member for which they were nominated by the COST National Coordinator, regardless of their nationality.
The main ideals of COST actions are:
- The bottom-up approach.
- ‘A la carte’, flexible participation.
- Inclusiveness and excellence.
- Acceptance of all partners, all career stages, and all countries.
- Excellence in science and technology.
- Support for Early Career Investigators (ECIs).
- Use of COST funding to leverage funding from nationally and regionally funded projects.
The consortium
Partner Countries
DARTER action brings together Members from 28 out of 38 COST Member Countries and Cooperating Member – Israel. In the Action participate also 3 International Partner Countries – Canada, China and United States.
