The DARTER COST Action uses networking and capacity building in the field of nucleic acid therapy delivery to allow RNA-targeting nucleic acid drugs to reach their full potential and become a mainstream therapeutic option. The DARTER objectives are clearly stated in the Memorandum of Understanding (MoU) and described on the COST web page. The DARTER Action started 23/10/2018 and will end 22/10/2022.

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Knowing that the ASO delivery field is fragmented, with researchers in academia and industry working in isolation on specific diseases, generally focusing on therapeutic effects in target tissues, DARTER Action aims to use networking and capacity building in the field of nucleic acid therapy delivery to allow RNA-targeting nucleic acid drugs to reach their full potential and become a mainstream therapeutic option. We aim to assess the state of the art and identify gaps in the knowledge to prioritize and align research efforts. This will be achieved by involving academics and industry working in ASO delivery in a kick-off meeting and drafting a whitepaper on the gaps of knowledge. We plan to develop SOPs for the use of models and procedures to assess delivery of ASOs, to improve comparison and reproducibility between groups. Task forces of experts will have dedicated planning workshops, comparing various procedures. We are going to achieve consensus on the use of models and procedures to assess safety and toxicity of ASOs to allow prioritization of chemical modifications and delivery compounds into preclinical and clinical studies. During the whole period of the DARTER Action we wil share unpublished results, particularly negative results, to avoid duplication of efforts and improve focus on effective compounds. During each workshop and conference of the Action, a special session will be organized on negative results. Furthermore, negative results will be published in a focus issue of a scientific journal.

Antisense oligonucleotides (ASOs)
are a new class of drugs that, through precise targeting, could correct genetic defects for rare inherited diseases, modulate autoimmune or neurodegenerative diseases or target tumours or viruses. They are short strands of DNA or RNA that can bind to RNA. Their act usually through binding (hybridisation, binding through Watson–Crick base pairing) to specific (target) sequences in coding RNA (pre‐mRNA or mRNA), so they are highly accurate. They can modulate the function of the target RNA. They can be manufactured at a large scale in a standardised manner. What more they do not need to be incorporated into genomic DNA with the use of viral vector as in case of other genetic therapies. There are different types of AONs, defined by their chemical structure, i.e. 20 O-methyl phosphorothioate oligonucleotides (2OMe), locked nucleic acids (LNAs), phosphorodiamidate morpholino oligomers (PMO) and peptide nucleic acids (PNAs). They can be bound with other compounds (moieties) to increase their delivery, such as cell-penetrating peptides (CPPs)

The elected Chair of the action is Prof. Virginia ARECHAVALA-GOMEZA, the Vice-Chair - Prof. Annemieke Aartsma-Rus and the Grant Holder - Leiden University Medical Center. The action Members are involved in one or more DARTER Working Groups, and each of the Working Groups is coordinated by two Working Group Leaders. COST Science officer Dr Inga DADESHIDZE and Administrative officer Ms Jeannette NCHUNG ORU supervise the DARTER Action performance.

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