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Overview

After performing initial proof-of-concepts for our DNA origami box, we will be validating the attachment of the DNA box to anti-CD3 antibody, the binding of the DNA box to prostate cancer cells, and finally, the ability of the DNA box to activate and recruit T-cells. The envisioned experiments and expected results are detailed below.

  • Following in vitro testing of our project, in vivo studies would be conducted to evaluate the efficacy and safety of our proposed design. In vivo testing would entail:
  • Selecting an animal model that closely mimics the pathogenesis of prostate cancer. Commonly used models include genetically engineered mice and xenograft mice models, where human cancer cells are implanted into immunocompromised mice
  • Evaluating different administration routes (e.g. intravenous injection, intratumoral injection, localized delivery) to determine the most optimal DNA box delivery method for targeting prostate cancer cells in vivo.
  • Quantifying efficacy of the drug in animal models and further R&D optimization as required
  • Gaining ethics approval by the Animal Research Ethics Board (Animal REB) and Canadian Council on Animal Care (CCAC) to conduct these studies

A thorough understanding of the DNA origami box’s pharmacokinetics, biodistribution, efficacy, and safety profiles will be developed through in vivo data. After undergoing a rigorous iterative process of modifying and refining the antibody-loaded DNA origami box based upon in vivo trial results, preparation can begin towards clinical trials.

Our design holds promise for advancing targeted and specific cancer therapies, with the long term goal of creating an effective, precise, and accessible treatment to improve patient outcomes and their quality of life.

References

Thomsen, M. K., & Busk, M. (2023). Pre-Clinical Models to Study Human Prostate Cancer. Cancers, 15(17), 4212. https://doi.org/10.3390/cancers15174212 Onaciu, A., Munteanu, R., Munteanu, V. C., Gulei, D., Raduly, L., Feder, R. I., Pirlog, R., Atanasov, A. G., Korban, S. S., Irimie, A., & Berindan-Neagoe, I. (2020). Spontaneous and Induced Animal Models for Cancer Research. Diagnostics (Basel, Switzerland), 10(9), 660. https://doi.org/10.3390/diagnostics10090660 Kelloff, G. J., Choyke, P., & Coffey, D. S. (2009). Challenges in clinical prostate cancer: Role of Imaging. American Journal of Roentgenology, 192(6), 1455–1470. https://doi.org/10.2214/ajr.09.2579