Funding opportunity

Funding opportunity: Addressing limitations in manufacturing nucleic acid therapeutics

Apply for funding to set up a research consortium addressing challenges in the manufacture of nucleic acid therapeutics.

Current manufacture challenges include but are not limited to:

  • scale of production
  • product purity, stereochemistry and reproducibility
  • sustainable production
  • novel chemistries
  • synthesis efficiency
  • analytical oligonucleotide characterisation.

The consortium can include academic and industrial organisations in the UK and abroad. The lead organisation must be UK-based.

Consortium proposals should demonstrate how the research outputs could benefit the wider UK research and manufacturing community.

You are encouraged to explore opportunities to collaborate with the Nucleic Acid Therapy Accelerator (NATA) Hub, a new research centre in the UK.

Who can apply

The opportunity will be open to academic, small and medium-sized enterprises (SME) and large industrial organisations based in the UK or abroad. The lead organisation must be UK-based. UK Catapults are eligible to apply as investigators.

Projects must be collaborative. At least two collaborators must be involved, including at least one partner commercially active in the nucleic acid therapeutics space. The lead organisation should be based in the UK.

Applications may include researcher co-investigators (RCoI) as set out in the MRC researcher co-investigator guidance.

What we're looking for

Opportunity for funding for early stage research and innovation to address current limitations to the large-scale manufacture of short (~20mer) nucleic acid therapeutics destined for clinical administration.

Funding available

This funding opportunity is part of the wider £30 million NATA programme, funded by the Strategic Priority Fund to support multidisciplinary approaches to the development of nucleic acid therapeutics (NAT). The programme is delivered by the Medical Research Council, part of UKRI, as part of a wider portfolio of support for advanced therapies.

Manufacture of NATs is currently complex, expensive and resource intensive, limiting large-scale production of these medicines. Despite improvements in product separation and reductions in stereoisomer by-products during chemical synthesis, purity remains a challenge.

New developments in solution-phase synthesis offer exciting opportunities to scale up, improve efficiency and reduce organic solvent use. Improved platforms for conjugation of targeting ligands hold promise for precision delivery and improvements in analytical characterisation remain crucial to regulatory confidence. This call will provide funding for a consortium to tackle these limitations.

Proposals must articulate a substantial, ambitious programme of work with clear potential to catalyse a step-change in UK NAT manufacture, having downstream translatability and wide-ranging industrial utility. Small-scale applications seeking to address specific issues tied to an existing asset or development programme are not eligible for this call.

At the full application stage, applicants will be required to demonstrate that the assembled team have the necessary experience, expertise and access to facilities to deliver the proposed research plan.

The principal investigator  should have demonstrable experience in leading large multi-investigator and multidisciplinary consortia or, at a minimum, applicants should demonstrate their potential to lead and manage a large-scale collaborative project.

Up to £6 million of UKRI funding will be available for two to five years to eligible academic organisations and SMEs. Leveraged funding and contributions in kind from industry partners, particularly via staff time and access to facilities, are welcomed. Large commercial entities should not request direct support.

Shortlisted applicants will be required to attend a workshop on 17 August 2021 prior to the submission of their full application.


To be within scope, proposals must address widely applicable limitations to large scale manufacture of short (~20mer) nucleic acid therapeutics destined for clinical administration through early stage research and innovation.

Proposals should also focus on at least one of the following:

  • development of new chemistries or technologies facilitating improved ability to manufacture at scale or form products with improved purity, stereochemistry and reproducibility (while the main focus of this call will be on chemical synthesis, conjugation and modification for short NATs, enzymatic methodologies will also be considered)
  • development of innovative liquid- or solution-phase synthesis technologies (applications seeking to develop outputs relevant only to solid-phase chemical synthesis are out of scope)
  • improved sustainability (for example, reduced requirement for organic solvents, improved product separation efficiency, a step change in chemistry efficiency)
  • development of oligonucleotide characterisation for analytical quality control
  • another limitation to the large-scale manufacture of NATs which is considered a priority by the expert review panel.


Applicants are encouraged to explore opportunities to collaborate with NATA Hub, a brand-new UK research centre offering end-to-end platform technology across the pre-clinical pathway, from oligo design, synthesis and characterisation, through to targeted delivery, in vitro screening and in vivo assessment.

NATA Hub, situated on the Harwell Research Campus, currently comprises chemistry and biology departments and an active portfolio of research projects making use of multidisciplinary, state-of-the-art infrastructure.

The chemistry department offers:

  • consultation on sequence design and chemical modification patterns of oligonucleotides:
    • small interfering RNA (siRNA)
    • antisense oligonucleotides (ASOs) gapmer and blockers
  • manufacture, purification and characterisation of natural and modified oligonucleotides, including:
    • new chemical modifications for nucleosides and nucleotides,
    • new modalities
    • ligands and conjugation methods of fluorescently-labelled oligonucleotides
    • detection and quantification of oligonucleotides in biological samples
  • expertise in detection and characterisation of trace impurities after synthesis or identification of metabolites after incubation or systemic injection via high-resolution mass spectrometry.

For a comprehensive overview of the hub’s capabilities and available equipment see Our Science (NATA Hub).

How to apply

This funding opportunity will involve a two-stage assessment process consisting of an initial expression of interest stage followed by a full application stage for invited applicants.

Expressions of interest

Expressions of interest (EOI) should be provided through the Joint Electronic Submission system (Je-S). Only the principal investigator will be required to register on Je-S at the initial expression of interest stage.

The EOI case for support form should be completed and uploaded to Je-S by 16:00 on 10 June 2021.

Expression of interest – Case for support form (109KB, DOCX)

This form will capture the underlying need and rationale of the manufacturing solution proposed.

Please ensure that all information provided in the EOI case for support form does not include identifiable information as this document will form part of our blinded peer review and scoring process during application triage. Expressions of interest with identifiable information will be returned for amendment.

Please refrain from including organisation name, location or investigator details in the case for support form at the expression of interest stage.

Investigator, researcher co-investigators and project partner information should be provided separately using the ‘applicant information form’.

When this document has been finalised, please ensure you name the document description as ‘Applicant Information form’ and upload to the Je-S attachments section of the outline proposal form, using the attachment type ‘Other Document’ (this will be for office use only).

Expression of interest – application information form (79KB, DOCX)

A separate CV should be uploaded onto Je-S for each investigator (two pages maximum). Uploaded CVs will be for office use only.

Letters of support are not required at this EOI stage.

To avoid possible document corruption, MRC would be grateful if all applicants would ensure attachments, for example case for support, CVs and other attachments, are uploaded to Je-S as PDF. All documents should be completed in single-spaced, Arial 11pt font or similar-sized sans serif typeface.

Applying through Je-S

You must apply through Je-S at the expression of interest stage and the full application stage.

When applying select:

  • council: MRC
  • document type: Outline Proposal
  • Scheme: Standard Outline
  • call/type/mode: Addressing limitations in manufacturing nucleic acid therapeutics EOI June 2021

After completing the application

You must ‘submit document’ which will send your application to your host organisation’s administration

Your host organisation’s administration is required to complete the submission process. Applicants should allow sufficient time for your organisation’s submission process between submitting your proposal to them and the call closing date.

Applicants should ensure they are aware of, and comply with, any internal institutional deadlines that may be in place.

MRC must receive your expression of interest by 16:00 on 10 June 2021.

How we will assess your application

Proposals will be assessed via a two-stage application process, with initial EOIs designed to capture key scientific opportunities to then be further developed through a more detailed full application. Assessment of applications will be via an independent panel of leading international academic and industry experts, closely supported by MRC head office.

Conflicts of interest will be managed according to MRC standard ways of working. External panel members will be under a non-disclosure agreement throughout the application process.

Expression of interest assessment

At the EOI stage, eligible submissions will be reviewed by expert panel members who will assess the unmet need identified in the proposal, alongside the proposed solution and associated rationale.

A strong expression of interest will meet the following assessment criteria:

  • clearly articulate a specific manufacturing barrier and a deliverable solution, describing how this will have a lasting impact on the sector
  • describe a credible approach with potential to result in a step change in approach, with downstream translatability and broad industrial utility beyond the consortium members
  • set out how project outputs would unblock development pipelines, evidencing a substantial potential pipeline of activity which might be enabled
  • demonstrate how the proposed solution will improve environmental sustainability and reduce chemistry-dependent toxicity
  • demonstrate the novelty and competitive advantage of the proposed solution with reference to alternative approaches
  • have freedom to operate and intellectual property assurances to enable the delivery of the proposal and the wider utility of outputs
  • demonstrate that the applicants are appropriately networked with the UK NAT landscape with particular reference to the NATA Hub.

Expressions of interest will go through the following assessment process.

  1. internal checks by MRC Head Office to confirm that investigators are eligible to apply and that expressions are within remit for this opportunity.
  2. EOI Case for support forms will be sent to expert panel members for peer review following management of any conflicts of interest.
  3. if necessary, applications will be shortlisted based on panel member comments depending on volume of applications.
  4. EOI Case for support forms will be discussed during a virtual triage meeting on 22 July, when nominated lead panel members will introduce the proposal, provide comment on its strengths and weaknesses and provide a recommendation for scoring. Proposals will be scored anonymously by each panel member based on the need of the proposed solution (scoring definitions available below) before proposals are ranked by the panel. The panel will aim to shortlist a manageable portfolio of full applications, being mindful that only one consortium can be supported.
  5. the full application process will launch with a virtual workshop on 17 August, which will be a compulsory requirement of the application process. Successful EOI applicants will be asked to present a non-confidential overview of their proposal to other applicants and invited representatives from leading international industry and academic organisations. Applicants may wish to form partnerships with other applicants or external organisations at this stage should it strengthen their proposal and increase their opportunity to successfully deliver the scheme’s objectives and envisaged impact.

Scoring definitions

High scoring proposals:

  • highly original and innovative
  • addresses a crucial scientific or technological capability gap
  • highly credible and realistic technical approach
  • potential for high impact to international NAT translation
  • well considered strategy for linking up with existing UK manufacturing initiatives.

Medium scoring proposals:

  • fairly original and innovative
  • address a scientific or technological capability gap
  • feasible technical approach
  • moderate impact to international NAT translation
  • some consideration demonstrated of how to link up with existing UK manufacturing initiatives.

Low scoring proposals:

  • evidence that other organisations have a competing solution
  • solution will provide limited scientific or technological capability
  • impractical or technically flawed approach
  • low impact to international NAT translation
  • very limited or no consideration demonstrated of how to link up with existing UK manufacturing initiatives.

Full application assessment

Immediately after the workshop, applicants will be invited to develop a full application setting out a detailed delivery plan for the proposed programme of work, including:

  • objectives
  • milestones
  • supplementary data
  • the consortium’s Heads of Terms collaboration agreement (including proposed management of background and arising intellectual property).

Integration of additional consortium members’ plans will be strongly encouraged at this stage, where complementary expertise to expand and strengthen initial plans can be drawn from the overall pool of applicants and the wider community. Further guidance on the full application stage will be provided to invited applicants.

Full applications will be peer reviewed by an independent expert panel with expertise covering the full range of the funding opportunity’s scope.

EOIs and full applications will not be sent for written peer review to external experts in the research community.


All applicants will receive written feedback following the panel discussion of their proposal.

Contact details

Prospective applicants may contact the NATA Challenges team to ensure their proposal is within scope before submitting at the EOI stage, providing a one page summary of the proposal (including an overview of the need, proposed solution and the programme’s primary objectives).


If you need help applying through the Je-S system, please contact the Je-S helpdesk:

Je-S helpdesk is staffed from Monday to Thursday 08:30 to 17:00 and Fridays 08:30 to 16:30 (excluding bank holidays and other holidays).

Additional info

NATA programme

The NATA is a £30 million investment awarded by the UK’s Strategic Priority Fund to support and accelerate the development of NAT. The NATA programme works in partnership with international industry and academic organisations and is being delivered by the Medical Research Council, part of UKRI.

The NATA programme consists of two main offerings to the UK R&I community:

  • the NATA Hub which offers world-leading, state-of-the-art NAT research infrastructure at the Harwell Research Campus, Oxfordshire
  • substantive programme grants to address a number of focused Research Challenges to tackle major barriers to NAT development.

The NATA programme is led by an Executive Group, chaired by Professor Fiona Watt who is the Programme SRO and Executive Chair of MRC, and supported by a world-leading Strategic Advisory Group (NATA Hub) that advise on strategic opportunities for the initiative.


NATA Hub is a brand-new UK research centre based on the Harwell Research Campus offering end-to-end platform technology across the pre-clinical pathway, from oligo design, synthesis and characterisation, through to targeted delivery, in vitro screening and in vivo assessment. NATA Hub comprises state-of-the-art chemistry and biology capability to collaboratively address bottlenecks in NAT development.

The hub is disease agnostic with an initial focus on short oligonucleotide therapeutics (ASOs and siRNAs).

NATA Hub’s toolbox and techniques will help answer the main questions about translational development:

  • target identification
  • oligonucleotides design and synthesis
  • off-target or safety prediction
  • precision targeting
  • ligand conjugation
  • efficacy in vitro or in vivo
  • distribution and uptake
  • quantification
  • drug metabolism and pharmacokinetics (DMPK).

NATA Hub’s initial areas of interest include tissue specific targeting, endosomal escape, novel manufacture methodologies and new advanced conjugate modalities.

NATA Research Challenges

NATA’s Research Challenge programme grants will enable and accelerate early stage innovation for nucleic acid therapy development, developing and disseminating platform technologies that will clear the way for the next generation of precision medicines.

Funding will support two consortia of academic and industry experts. One consortium will address barriers to the manufacture of synthetic nucleic acid therapeutics and one consortium will address barriers to precision delivery. Up to £6 million of UKRI funding will be available to each consortium.

NATA’s second Research Challenge funding opportunity will launch later this year, supporting systemic targeting and intracellular delivery of nucleic acid therapeutics.

Industry involvement and available funding

MRC is keen for industry to be actively involved in consortia and, whilst we expect that large companies would support their own costs in participating in the consortia, we are willing to consider requests for funding from small/medium companies involved in the consortia.

These requests will be reviewed on a case-by-case basis and will need to be accompanied by an explanation at the full application stage as to:

  • why the involvement of the company is essential to the success of the consortia
  • how the funding to the company will be used to support the objectives of the consortia
  • why the company is not able to support the costs themselves.

We may also undertake financial checks on companies requesting funding to ensure that the company is not in financial difficulty. MRC reserves the right to adapt the funding model available to companies to comply with future UK subsidy control rules. If this is necessary, MRC will communicate with applicants during the application process.

Intellectual property guidance

MRC recognises that intellectual property (IP) considerations will vary across each individual consortium and we support the formation of appropriate governance structures that principally facilitates the delivery of a programme’s science, while managing background and arising IP for the benefit of the consortium and the UK.

As such, MRC will expect each consortium to put in place a collaboration agreement before MRC provides funding to the successful consortium.

Whilst the exact provisions included in the agreement will require discussion by the consortium, MRC has some principles in relation to the management of IP which it expects to be taken into consideration. These principles can be discussed in more detail during the application process.

To summarise, the collaboration agreement should ensure that each partner has the rights to use any background and arising IP to deliver the research planned by the consortium.

MRC would expect the consortium to jointly agree and co-ordinate the protection and commercialisation of arising IP, taking into consideration how access to background IP may be achieved if needed for commercialisation and ensuring that academic consortium members and the wider academic community are and remain able to use arising IP.

Dependent on contributions made, it may be appropriate for industry consortium members to be granted rights to use arising IP for internal research purposes and an option mechanism to take licences for commercial purposes.

However, MRC would expect that any arising IP that is of general applicability and utility would only be licensed non-exclusively for commercial purposes to ensure the widest possible impact.

Additional conditions

Supplementary to the standard UKRI grant conditions, additional conditions will be added to this call. These will include, but are not limited to the following conditions.


This award is contingent upon meeting the progression milestones set out at the full application stage. Failure to meet progression milestones may result in termination of the award at the discretion of MRC. Spending on the grant should be limited to work detailed within the programme plans for the active milestone.

Without specific prior written approval, MRC will not reimburse the host institution for the costs of any work contributing to a later milestone should it be decided that the criteria of an active milestone have not been met and the programme is terminated.

Changes to programme plan

If issues or problems arise prior to or during the course of the funded programme that could potentially result in the inability to achieve the programme objectives or milestone, the issue, as well as proposed solutions, should be promptly communicated to MRC.

MRC requires that the programme team provide advance notification of any proposed change to the programme plan, including significant changes in milestone criteria, grant length or cost, in writing. Requests may be sent to

Changes must be approved by the MRC prior to them being implemented. Please note, due to the milestone driven nature of the project, the process for change requests differs from other MRC schemes. Please do not submit your request through Je-S.

Expenditure against grants

The duration of the grant should be between two and five years. Expenditure profiles will be agreed before the programme commences.

Reporting and expenditure profiles

The awarded consortium must provide quarterly progress reports reporting the programme’s delivery against objectives, success criteria and milestones. Financial reporting on to-date and forecast expenditure, in addition to risks to delivery, will also be captured in quarterly reports.

It is the responsibility of the host organisation to ensure the research programme remains on the expected profile. Research organisations must inform MRC of material slippage or cost savings as soon as possible. MRC reserves the right to suspend or reprofile a grant if spend does not closely match allocation.

External advisory board

Grant holders must establish an external advisory board, or equivalent body, to act as a ‘critical friend’ and provide advice on the running of the project, its research and related activities. This board must meet with grant holders at least annually, with the grant holders providing the external advisory board with an annual written report before the meeting detailing the project’s:

  • progress against programme objectives and milestones
  • risks and mitigation strategy
  • outputs and training
  • outreach and professional development activities.

Each advisory board meeting will include UKRI observers and will be chaired by the NATA Executive Director when in post. NATA or MRC will provide secretariat for the external advisory board.

Commercialisation committee

Grant holders must establish a commercialisation committee with representation from all consortium members and NATA to coordinate the protection and commercialisation of arising IP, including approval of commercialisation agreements.

Final expenditure statement

It is the responsibility of the principal investigator to submit a final expenditure statement and a Project End Report at the end of the grant. The final payment will be withheld until the final expenditure statement and the Project End report are received and failure to submit may result in financial sanctions.

Evaluation requirements

This funding opportunity is part of the wider NATA programme, funded by the Strategic Priorities Fund (SPF). In line with the SPF’s business case, the NATA programme and grant holders funded by the programme must adhere to the evaluation requirements set by the SPF.

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