Call for proposals: RNA-based therapeutics for neurological disorders

Disruptive Technology Solutions for Cell and Gene Therapy Challenge program

1. Program details

The National Research Council of Canada's (NRC) Disruptive Technology Solutions for Cell and Gene Therapy Challenge program is launching a call for proposals to create collaboration opportunities between the NRC and the broader research community. Collaborations would unify the value chain for engineered cell and gene therapies, from discovery to commercialization.

In 2018, the NRC launched the challenge program to develop a collaborative framework by aligning with multiple partners and collaborators from various sectors, to address critical health challenges facing Canadians.

1.1. Vision and mission

The program's vision is to transform health outcomes for Canadians with cancer and genetic diseases. Our researchers use synthetic biology-driven innovations in engineered cell and gene therapies to bring this vision to life.

The program's mission is to develop technologies, platforms, cell lines and collaborative models that will speed up development and enable the delivery of safe, accessible and affordable cell and gene therapies in Canada.

1.2. Addressing challenges

To address specific challenges in the cost-effective development and clinical delivery of gene therapies for disorders of the central nervous system, the program is seeking a collaborative partner to support the preclinical translation of a made-in-Canada RNA-based therapeutic for the treatment of neurological disorders.

2. Objectives

The NRC owns key technologies for the successful brain delivery of RNA therapeutics, including brain-targeting antibodies and proprietary lipid-based nanoparticles.

We have extensive knowledge and expertise in formulation and bioconjugation technologies. For example, using receptor-mediated transcytosis with brain-targeting antibodies allows us to efficiently transport lipid-based nanoparticles containing nucleic acid cargoes across the blood-brain barrier. Leveraging these technologies, we have developed a panel of blood-brain barrier-transmigrating antibodies, allowing the delivery of RNA therapeutics to the brain for gene expression, silencing and editing of central nervous system targets.

The proposed collaboration aims to encapsulate therapeutics in our proprietary brain-optimized lipid-based nanoparticles for detailed preclinical studies, laying the foundation for future clinical trial applications.

To achieve our objectives, we are seeking a 2-year collaboration to:

  • leverage collaborator experience in an intracellular brain gene target to design potent RNA therapeutic drug candidates
  • encapsulate the selected RNA therapeutic into our proprietary brain-optimized lipid-based nanoparticles and evaluate potency and toxicity in vitro
  • conduct detailed in vivo preclinical therapeutic efficacy and toxicity studies using a relevant animal model of central nervous system disease, using a range of doses and dosing frequencies
  • create a robust preclinical data package to de-risk technology for future pharmaceutical partners and support clinical trial applications

3. Eligible projects and teams

Collaborators working with the NRC who are eligible for funding under this call:

  • Canadian small and medium-sized enterprises (those with fewer than 500 employees)
  • Not-for-profit research organizations
  • Research institutions
  • Academic institutions

Preference will be given to Canadian collaborators. International applicants may be considered.

Requirements:

Note: Un-funded collaborators and subcontractors from across the technology ecosystem may also collaborate on projects.

3.1. Commitment to EDI and GBA+

Project teams must clearly demonstrate their commitment to equity, diversity and inclusion (EDI) and gender-based analysis plus (GBA+) in their research applications, including composition of their project teams, research methods, analysis and knowledge-mobilization plans. Undertaking GBA+ and critically considering factors related to EDI adds valuable dimensions in research and improves the quality, social relevance and impact of the research.

In addition, it may contribute to taking the research in a new direction. EDI and GBA+ considerations should influence all stages of research or development processes, from establishing priorities and building theory to formulating questions, designing methodologies and interpreting data. Applicants are invited to consult the guide to best practices in equity, diversity and inclusion in research practice and design.

4. Costs

Eligible costs:

  • Salaries for highly qualified personnel working on the project activities
  • Research support costs (direct costs incurred in the project implementation phase), including:
    • consumable materials
    • supplies
    • equipment rentals
    • facility rentals
  • Costs for on-duty travel required to execute the project and limited conference travel (for highly qualified personnel)
  • Amounts invoiced to the applicant by a contractor for services rendered relating directly to the project (e.g., professional services fees)
  • Indirect costs that are not directly applicable to carrying out the project but necessary to conduct the recipient's general business, up to a maximum of 10% of total eligible costs
  • Equipment costs
    • Laboratory equipment and other components, generally between $10k and $50k

Equipment costs must not exceed 25% of the Collaborative Science, Technology and Innovation program's project funding. Applicants must show that the project objective may not be achieved without this equipment and that equipment can be procured in a reasonable timeframe.

Costs not covered:

  • Purchase of land
  • Leasehold interest
  • Property taxes
  • Any portion of costs subject to refunds, rebates or credits, including HST, GST and PST
  • Costs paid by the NRC

5. Funding and support

Funding provided by the National Program Office follows the terms and conditions of the Collaborative Science, Technology and Innovation program. This program is intended to position the NRC as a collaborative platform that uses science excellence to respond to Canada's most pressing challenges.

As such, projects supported under this initiative benefit from NRC assets in place (special-purpose research facilities, scientific expertise and networks) and financial assistance in the form of non-repayable grants or contributions.

For more information on available funding, consult the grant and contribution funding for collaborators webpage.

The program is planning to make $500,000 available to support 1 project under this call with a 1:1 matching contribution (cash or in-kind) from the selected collaborator.

All deliverables must be addressed and the funding must be spent by the end of the program on March 31, 2026. There will be no project extensions beyond this date.

5.1. Stacking provisions

The stacking provisions for projects are as follows:

  • The maximum limit of the total Canadian government assistance (federal, provincial, territorial and municipal assistance for the same eligible costs) cannot exceed 100% of the total eligible project costs
  • The maximum NRC cost share will not exceed 50% of total eligible project costs

6. Application process and timelines

The NRC is committed to a consistent, fair and transparent selection process to identify, select and approve the allocation of funding to projects that best fit the objectives of the collaborative call.

Expressions of interest will be assessed based on the following technical requirements and the criteria provided in Annex A.

6.1. Technical requirements

  • Significant and proven experience in central nervous system disease target selection
  • A strong track record in both in vitro and in vivo evaluation of brain therapeutics for animal models of central nervous system disease

Proposals will be evaluated based on the strength of the approach, expertise of the team and technical feasibility by an expert review panel.

6.2. Key dates and deadlines

  • November 15, 2023: Call opens
  • December 5, 2023 Q&A with the NRC research team (requires registration)
  • January 22, 2024: Proposal submission deadline
  • April 2024: Successful projects move to the next stage

6.3. Registration

Register for this call and the Q&A session by sending an email to NRC.HealthProgram-ProgrammeSante.CNRC@nrc-cnrc.gc.ca  

7. Projects and funding agreements

After receiving the notice of project approval, applicants must enter into a collaborative research agreement with all project collaborators or a funding agreement (non-repayable transfer payment) with the NRC. If an agreement cannot be finalized within a reasonable timeframe, funding may be cancelled.

8. Contact information

For more information on this specific collaboration opportunity with the Disruptive Technology Solutions for Cell and Gene Therapy Challenge program, please send an email to: NRC.HealthProgram-ProgrammeSante.CNRC@nrc-cnrc.gc.ca

Annex A: Proposal evaluation criteria

The proposals will be assessed using the following criteria.

Team composition

  • The project team has an applicant principal investigator from an organization that is eligible to receive funding from the NRC
  • Principal investigators are identified from each collaborating organization and their role in meeting the project deliverables is clearly defined
  • The team demonstrates expertise and experience in CNS disease target selection, RNA therapeutics and brain therapeutic development for animal models of central nervous system disease
  • The team has a track record in both in vitro and in vivo evaluation of brain RNA therapeutics

NRC collaboration

  • The project aligns with the NRC's key technologies, such as brain-targeting antibodies, NRC proprietary brain optimized lipid-based nanoparticles, and bioconjugation technologies
  • The collaboration leverages the NRC's assets and resources, including scientific expertise, networks, and research facilities
  • The collaboration is feasible in terms of implementing NRC's technologies and achieving the project's objectives

Alignment

  • The project aligns with the objectives of the Disruptive Technology Solutions for Cell and Gene Therapy Challenge program, particularly in terms of developing RNA therapeutics for central nervous system diseases
  • The project aligns with the NRC's proprietary brain-optimized lipid-based nanoparticles and other technologies
  • The project has the potential impact and transform health outcomes for Canadians with brain diseases
  • The project description fits within the available timeline
  • The project supports the attainment of benefits for Canada

Quality

  • The project has a sound research approach and clearly articulates the scientific and business rationale for target selection and methodology
  • The proposed RNA therapeutic drug candidates are innovative
  • The project has a high likelihood to impact the field of gene therapy

Eligibility

Funding

  • Adequate rationale is provided for financial assistance of the recipient
  • The funding recipients are eligible based on the Collaborative Science, Technology and Innovation program guidelines
  • The applicant team can commit a minimum of 1:1 matching funds (cash or in-kind)
  • The project costs are eligible