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Oligonucleotide Backbone Modifications

Objective

Therapeutic oligonucleotides are rapidly emerging as novel modalities for the treatment of several previously unaddressable diseases. The development of oligonucleotide therapeutics has thereby been significantly driven by chemical modifications that enhance nuclease resistance, pharmacokinetic properties, and target engagement. Especially the modification of the phosphorus site at the internucleoside linkage, in particular by the replacement of an oxygen with sulfur in the form of phosphorothioates, proved to be decisively beneficial. However, despite the immense and immediate impact, the current phosphorus backbone chemistry to form modified functionalities, such as phosphonates and phosphoramidates, remained severely limited by the classical reactivity at phosphorus. Expanding the chemical space of oligonucleotide backbone modifications requires transformations that can operate under mild conditions compatible with sensitive nucleic acid substrates. Here, we propose to explore the innovation potential of an unusually versatile method for oligonucleotide backbone modification developed in the framework of an ERC-CoG funded project. With the intellectual property protected by the filing of four patent applications, this Proof of Concept project aims to explore a stereoselective library creation by the divergent synthetic backbone modification platform. The method already allows linear and parallel synthesis from commercially available nucleosides via standard phosphoramidite synthesis and avoids the purification of sensitive intermediates. Efforts in this PoC will be focussed on diastereoselective oligonucleotide backbone modifications, the corresponding IP protection, licensing of the innovation as part of research collaborations with the pharmaceutical industry, and the creation of a spinout company.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2026-POC

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Host institution

UNIVERSITAT BASEL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
PETERSPLATZ 1
4051 Basel
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Beneficiaries (1)