Challenge accepted: how the NRC is helping Canadians living with rare diseases

- Ottawa, Ontario

The NRC’s Disruptive Technology Solutions for Cell and Gene Therapy Challenge program is developing solutions for precision-engineered cell and gene therapies which could treat and potentially cure chronic diseases and rare genetic disorders affecting Canadians.

The NRC is also advancing delivery solutions to make cutting-edge cell and gene therapies more accessible and affordable for Canadians.

Researchers from the Challenge program have made significant headway over the past year in setting up critical foundational investments and key initial collaborations.

The program has established and continues to establish collaborative partnerships to support and leverage the Canadian value chain and enable clinical use of accessible, affordable and Canadian-made gene therapies that target genetic diseases, and cell therapies that target cancer.

The program also aims to use disruptive technologies on biological therapeutic platforms, to accelerate discovery, development, manufacturing and translation to clinical trials.

Collaborations on gene therapy for lipoprotein lipase deficiency

The program team established a key partnership in 2020 to collaborate on the creation of a made-in-Canada gene therapy for lipoprotein lipase deficiency (LPLD), which is a rare genetic disorder causing chronic stomach pain that can lead to pancreas and liver problems, and eventually diabetes. By partnering with the University of British Columbia’s Drs. Michael Hayden and Colin Ross, they will accelerate optimizing and pre-clinically validating an adeno-associated virus-based (AAV) gene therapy for LPLD, which will be manufactured for clinical testing using the NRC’s manufacturing design process.

Key to this project is NRC’s collaboration with the Ottawa Health Research Institute (OHRI), which has received NRC contribution funding. This collaboration will allow OHRI to leverage their viral expertise and good manufacturing practice know-how to establish unique capacity to produce AAV gene therapy vectors, such as Challenge program’s lead gene therapy (e.g. AAV-LPLD vector). This foundational investment is critical to proving that the Canadian ecosystem has the capacity to produce therapeutic gene therapy vectors that can be delivered to patients with rare genetic diseases through clinical trials.

The LPLD project will be an important example of how we can use a disruptive delivery model for gene therapies for rare diseases through the leveraging of various partnerships, including government-to-government and government-to-private partnerships.

Experts report on considerations in approving and using cell and gene therapies

While cell and gene therapies are promising for treating rare genetic disorders and chronic diseases, the use of these therapies could raise several challenges, including regulatory barriers, equity in access to treatment, and affordability.

To support implementing these and other therapeutic platforms that could emerge from this program, the NRC commissioned a report by the Canadian Council of Academies to gather expert opinions on social, ethical, legal and regulatory hurdles to approving and using somatic gene therapies in Canada.

Published in November 2020, the report will be discussed publically at the 2020 Gairdner Ontario International Symposium “Breaking Through: Delivering on the Promise of Gene Therapy”.

Developing capacity for mammalian genome editing

The Disruptive Technology Solutions for Cell and Gene Therapy Challenge program team also made another critical foundational investment with Concordia University’s Centre for Applied Synthetic Biology to develop novel and world-class capacity for mammalian genome editing. Ultimately, the vision is to capitalize on this new capacity to accelerate engineering of cells with greater precision, enabling the addition of novel safety and therapeutic attributes in cell-based therapies.

This will allow NRC researchers, along with collaborators, to demonstrate the potential to establish progenitor stem cell lines engineered with critical safety and immune tolerance features, which are key barriers to successful use of these promising therapies in patients.

What’s next for the program

Following the example of the LPLD gene therapy project, the program team will establish a parallel model to provide a pathway to patient access for chimeric antigen receptor (CAR) T cell therapies. This will involve an infrastructure investment in distributed cell manufacturing expansion in other labs across Canada, and launching a clinical trial to evaluate an NRC-made CAR-T for hematologic malignancy.  CAR-T is an engineered cell platform used successfully to date in treating specific blood cancers. It involves taking a patient’s blood cells, purifying immune killer cells, and engineering them with genetic sequences that reprogram the cells to attack the patient’s cancer. Future research in program aims to direct this engineered cell platform into the arena of therapy for solid cancers.

The Disruptive Technology Solutions for Cell and Gene Therapy Challenge program team expects to engage in further collaborations to advance component design and validation for a microfluidic-scale automated cell engineering platform. This would be done in parallel with the launch of projects to optimize cell manufacture and analytics for personalized cell products. These new projects will provide critical proof of concept for novel disease-targeting and potentially multi-targeted CAR-T therapies, antibody-coupled nanoparticles, and other strategies of the future. Grant and contribution funding is available for eligible collaborators who offer complementary expertise for NRC collaborative projects.

The Challenge programs are part of a suite of collaborative R&D initiatives bringing together researchers and facilities from across the NRC's 14 research centres with academic, not‑for‑profit and industrial partners.

Learn how the NRC is leading the way on a variety of disruptive R&D technologies to address issues that affect us today, tomorrow, and in the long term.

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