Funding opportunity

Funding opportunity: Early ideas to improve the delivery of nucleic acid therapeutics

Apply for funding to improve the delivery of nucleic acid therapeutics (NAT).

We expect to fund one consortium. We will fund:

  • small or medium-sized enterprises (SME)
  • academic organisations
  • public sector organisations.

Your consortium can include large businesses but they cannot request funding.

The principal investigator must be UK based. At least one partner must be commercially active in NAT in the UK.

The other partners can be based anywhere in the world.

The first stage is an expression of interest and you do not need detailed plans or an exact budget to apply. We’ll run a workshop to help successful applicants get ready for the full application stage.

Who can apply

The opportunity is open to academic and industry organisations based in the UK or abroad. The lead organisation must be UK based.

To apply for funding you must be one of:

  • academic organisation
  • SMEs
  • eligible public sector research establishment (PSRE)
  • UK Catapult.

Large industrial organisations can apply as investigators but not request funding.

Check your organisation is eligible for funding.

Projects must be collaborative. At least two organisations must be involved, including a minimum of one partner commercially active in the nucleic acid therapeutics space in the UK.

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

Find partners

To facilitate connections between prospective applicants from across the community when forming a consortium, we have set up the NATA delivery research challenge LinkedIn group. You’re encouraged to join if you wish to seek potential collaborators with shared or complementary interests.

You do not need to have all your partners agreed when you submit your expression of interest. If you’re invited to submit a full application, there will be a workshop to help you find partners.

Experience needed

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 multi-investigator and multidisciplinary consortia or, at a minimum, applicants should demonstrate their potential to lead and manage a large-scale collaborative project.

What we're looking for

This funding opportunity is part of the £30 million Nucleic Acid Therapy Accelerator (NATA) programme, funded by the Strategic Priorities Fund. The NATA programme supports multidisciplinary approaches to the development of NATs. The programme is delivered by MRC, part of UKRI, as part of a wider portfolio of support for advanced therapies.

The promise of NATs has been demonstrated in the clinic. However, their development and widespread use has been hindered by a lack of robust techniques to achieve targeted delivery to specific tissues, improve stability and facilitate uptake into cells, without compromising on safety or effectiveness.

This funding opportunity will support a consortium to tackle major barriers to safe and effective NAT delivery through the development of:

  • novel technologies
  • platforms
  • resources.

To solve these challenges, new approaches could arise from any scientific discipline or therapeutic modality.

At the expression of interest stage you should provide an overview of:

  • the unmet need
  • your proposed solution
  • the associated rationale
  • an estimated overall budget.

At the full application stage we will require:

  • detailed plans and milestones
  • supporting evidence
  • a full list of consortium partners
  • a full budget breakdown
  • details of intellectual property (IP) arrangements.

Scope of your proposal

To be within scope, proposals must articulate a substantial, ambitious programme of work with clear potential to catalyse a step change in the delivery of NATs.

Transformative opportunities could include, but are not limited to:

  • platform technologies or tools to enable more efficient, safe and effective delivery of NATs and more reproducible research and development, including but not limited to:
    • models, tools, methods and technologies to support robust, standardised assessment and analysis of NAT uptake, distribution and activity
    • approaches to improve the likelihood of successful translation between in vitro and in vivo, between species and into humans
    • bioinformatic approaches and resources to support accurate prediction of safe and efficient delivery mechanisms
  • activities enabling improved active uptake and intracellular trafficking of NATs
  • innovative strategies addressing unmet needs in targeting of specific organs, tissues or cell types, including via:
    • chemical modification
    • conjugate moieties
    • alternative chemistries.

Novel technologies or major patient-centred improvements enabling non-systemic delivery of NATs, in other words direct administration strategies, will be within scope where they have significant primary relevance to a broad pipeline of NATs.

Stage of research

While the focus of the consortium’s research plan should be early-stage and applied pre-clinical research and innovation, proposals can include basic research where this would directly enhance the translational outputs of the consortium, for example:

  • elucidating mechanisms of cellular uptake, endosomal escape and intracellular localisation
  • research around safety of NAT delivery mechanisms, immunogenicity and impacts of chronic dosing, which will enable an improved balance of efficacy and toxicity
  • heterogeneity between cell types, disease states and species specific to its impact on NAT delivery
  • effects of saturation of receptors or cellular trafficking machinery, including mechanistic toxicity.

Outputs

Proposals should clearly articulate how the consortium’s outputs will:

  • have downstream translatability
  • demonstrate wide-ranging industrial and academic utility
  • improve the reproducibility of early stage research and innovation
  • take account of:
    • safety and toxicity
    • scalability
    • manufacturing
    • cost
    • quality control
    • regulatory issues
    • other considerations relevant to the development of NATs destined for clinical administration.

What we won’t fund

The following activities will not be within scope:

  • small-scale applications seeking to address specific issues tied to an existing asset or development programme
  • programmes focusing solely on the delivery of modalities that require the translation of the delivered product to exert a therapeutic effect
  • programmes where the impact will be limited to a particular clinical indication
  • programmes where the output will primarily support delivery of mRNA vaccines
  • programmes focusing on delivery to hepatocytes
  • programmes developing delivery systems without direct relevance to precision delivery of NATs
  • programmes comprising mainly basic research or without a significant applied component
  • late-stage development or clinical studies of NATs or delivery systems.

Funding available

There is no funding in this expression of interest stage.

In the full application stage, up to £6 million of UKRI funding will be available for up to three years to eligible:

  • academic organisations
  • SMEs
  • PSREs
  • Catapults.

We expect to fund one consortium. Standalone small-scale applications will not be supported. After shortlisting, the expert review panel may suggest combining or augmenting smaller proposals to maximise impact.

Leveraged funding and contributions in kind from industry partners, particularly via staff time and access to facilities, are welcomed.

MRC will support programme costs at 80% of the full economic cost as standard. Some exceptions will be considered for support at 100% full economic cost where fully justified at the full application stage, including:

  • eligible research costs incurred by SMEs, PSREs and Catapults
  • eligible costs of research being conducted outside the UK, where the required expertise cannot be sourced within the UK.

Large commercial entities should not request direct support.

NATA Hub

Applicants are expected to explore opportunities to collaborate with NATA Hub, a new UK research centre offering innovative approaches across the pre-clinical pathway. NATA Hub experts can contribute to collaborations through, for example:

  • oligo design, synthesis and characterisation
  • in vitro screening
  • vivo assessment of safety, distribution, and efficacy.

NATA Hub, situated on the Harwell Research Campus, currently comprises chemistry and biology departments and a portfolio of research projects making use of multidisciplinary, state-of-the-art infrastructure. Further information about the NATA programme can be found in ‘additional information’.

Learn more about NATA Hub

How to apply

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

Check your proposal is in scope

Applicants are encouraged to contact MRC to ensure their proposal is within scope before submitting an EOI. Provide a one page summary including an overview of the need, proposed solution and the programme’s primary objectives to challenges@natahub.org.

Expressions of interest

EOI must be submitted by email to challenges@natahub.org. We must receive your application by 6 January 2022 16:00 UK time.

The following documents are required as attachments in PDF format. Letters of support, heads of teams and other documents are not required or permitted at the EOI stage.

EOI case for support form

One per application.

Please ensure that the EOI case for support form does not include identifiable information (such as organisation names, locations or investigator details). This document will form part of our blinded peer review and scoring process during application triage.

Download the case for support form (DOCX, 81KB).

EOI applicant information form

One per application.

Investigator, researcher co-investigator and project partner information should be provided separately using this form, which will not be made available to reviewers.

Download the EOI applicant information form (DOCX, 82KB).

CV for each investigator

Two pages maximum for each CV.

These will not be made available to reviewers.

If you’re shortlisted

Shortlisted applicants will be required to attend a workshop on 2 March 2022 prior to the submission of their full application. This will be an opportunity to develop collaborations and project plans in response to panel feedback. Investigators will present a non-confidential overview of their proposal. Applicants may wish to form partnerships with other applicants, external organisations or both at this stage, should it increase their opportunity to successfully deliver the programme’s objectives and impact.

Integration of additional consortium members’ plans will be strongly encouraged at this stage. Complementary expertise to expand and strengthen initial plans can be drawn from the overall pool of applicants and the wider community.

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
  • supporting data
  • the consortium’s heads of terms collaboration agreement (including proposed management of background and arising IP).

Further guidance on the full application stage will be provided to invited applicants.

How we will assess your application

A panel of leading international academic and industry experts will assess proposals in a two-stage application process. Initial EOIs are designed to capture key scientific opportunities, with shortlisted EOIs being invited to develop a more detailed full application.

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. Applications will not be sent out for peer review.

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

Assessment criteria

A strong EOI will broadly meet the following assessment criteria:

  • clearly articulate a specific 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 the field, with downstream translatability and broad industrial and academic 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 the novelty and competitive advantage of the proposed solution with reference to alternative approaches
  • incorporate an appreciation of factors crucial for future development of NATs enabled by this solution, including safety, manufacturing, cost, quality control and regulatory considerations where relevant
  • indicate that freedom to operate and IP assurances will be in place 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 NATA Hub
  • present a clear opportunity for public funding to make a significant impact, including the potential for leveraged input (financial or in-kind) to maximise the available resource.

Assessment process

EOIs will go through the following assessment process.

  1. Checks by MRC head office to confirm that investigators are eligible to apply and that expressions are within remit for this opportunity. Applications outside the remit or that contain identifiable information in the case for support may be rejected at this stage.
  2. Anonymised 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 to manage the volume of applications to be considered at the panel meeting, proposals might be rejected based on panel members’ written comments.
  4. Anonymised EOI case for support forms will be discussed during a virtual triage meeting on 7 February 2022. Each proposal will be discussed and then scored anonymously by each panel member based on the need and innovation of the 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 of the demand on the available budget.
  5. All applicants will receive written feedback.

Scoring

High scoring proposals:

  • highly original and innovative
  • address 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 positioning within the existing UK NAT landscape.

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 the activity would fit within the UK NAT landscape.

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 the activity would fit within the UK NAT landscape.

Full application assessment

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

Contact details

Ask about this funding opportunity

For further information or to discuss a potential proposal with MRC.

Email: challenges@natahub.org

Include ‘NAT delivery funding opportunity’ in the subject line.

We aim to respond within five working days.

Ask about the NATA Hub

Email: enquiries@natahub.org

Include ‘NAT delivery funding opportunity’ in the subject line.

Additional info

Supporting documents

Case for support form (DOCX, 81KB)

Applicant information form (DOCX, 82KB)

Expression of interest stage shortlisting panel (PDF, 46KB)

Full application stage applicant guidance (PDF, 214KB)

NATA programme

The Nucleic Acid Therapy Accelerator (NATA) is a £30 million investment awarded by the UK’s Strategic Priorities 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 MRC, part of UKRI.

The NATA programme consists of two main offerings to the UK research and innovation community:

  • the NATA Hub, which offers world-leading, state-of-the-art NAT research infrastructure
  • substantive programme grants to address two focused research challenges representing major barriers to NAT development.

About the NATA Hub

NATA Hub is a new UK research centre based on the Harwell Research Campus, Oxfordshire. It 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. This includes antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs).

NATA Hub’s initial areas of interest include:

  • tissue specific targeting
  • endosomal escape
  • novel manufacture methodologies
  • new advanced conjugate modalities.

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

  • consultation on sequence design and chemical modification patterns of oligonucleotides:
    • siRNAs
    • ASOs, gapmer and blockers
    • aptamers
  • manufacture, purification and characterisation of natural and modified oligonucleotides, including:
    • new chemical modifications for nucleosides and nucleotides
    • new modalities, including new ligands and conjugation methods
    • fluorescently labelled oligonucleotides for microscopy
    • 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
    • expertise in assessing pre-clinical issues relating to toxicology, tissue distribution, efficacy, specificity, and drug metabolism and pharmacokinetics (DMPK)
    • fine-grained analysis of spatial distribution within tissues
    • fine-grained analysis of cell type specific uptake and efficacy
    • high throughput transcriptome-wide off-target and toxicity profiling
    • high throughput in vitro screening (efficacy and toxicity)
    • DMPK.

There will be a workshop on 2 March 2022 where shortlisted applicants will have the opportunity to:

  • meet NATA representatives
  • hear more about the NATA Hub’s capabilities and available equipment
  • learn how to explore options for collaboration.

NATA Research Challenge programme

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.

A total of up to £12 million funding will support two consortia.

One consortium will address limitations in the manufacture of synthetic NATs. The manufacture research challenge funding opportunity is in progress and the successful consortium award will be made in early 2022.

The second research challenge addressing barriers to NAT delivery is represented through this funding opportunity.

Industry involvement and available funding

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

IP guidance

MRC recognises that IP considerations will vary across each consortium. We support the formation of appropriate governance structures that principally facilitate 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 coordinate the protection and commercialisation of arising IP. It will take 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.

Depending 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 or 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 funding opportunity. These will include, but are not limited to the following conditions.

Milestones

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 challenges@natahub.org.

Changes must be approved by 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.

Reporting and expenditure profiles

Expenditure profiles will be agreed before the programme commences.

The awarded consortium must provide quarterly progress reports covering 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 consortium, its research and related activities.

This board must meet with grant holders at least annually. Before the meeting the grant holders must provide the external advisory board with an annual written report, 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. 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. In line with the fund’s business case, the NATA programme and grant holders funded by the programme must adhere to the evaluation requirements set by the fund.

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