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Goals & Success Criteria

Our Criteria for Success

DNA Origami Box Design

  • Box is thermodynamically stable
  • Box design is capable of docking anti-CD3 antibody
  • Box has a viable lock and key mechanism
  • Anti-CD3 antibody successfully attaches inside of box

Evaluation of Target Specificity to Prostate Cancer Cells

  • Anti-CD3 antibody binds to T cells
  • Box + anti-CD3 antibody binds to T cells
  • Design RNA aptamer that binds to PSMA receptor (aptamer 1)
  • Box + aptamer 1 binds to PSMA receptor

Validation of Function Upon Binding to Prostate Cancer Cells

  • T cells are recruited by box + anti-CD3 antibody + aptamer
  • T cells are activated by box + anti-CD3 antibody + aptamer
  • Box + anti-CD3 antibody + aptamer 1 opens upon binding to PSMA receptor
  • Box + anti-CD3 antibody + aptamers 1 and 2 opens upon binding to both PSMA and NTSR1 receptors
  • In vitro testing using LNCaP cells

Objectives

The objectives for this project are as follows:

  1. Designing and synthesizing an appropriate DNA Origami Box via DNA/RNA nanostructure tools, and validating the formation of our DNA origami box using gel electrophoresis and TEM

  2. Attaching the anti-CD3 antibody to the box via antibody docking, and validating the attachment of the anti-CD3 antibody by gel electrophoresis and TEM

  3. Verifying that our chosen aptamer binds to PSMA with ELISA

  4. Confirming that our chosen anti-CD3 antibody binds to T-cells using flow cytometry

  5. Verifying that the box will bind to prostate cancer cells and open via flow cytometry

  6. Checking for T-cell activation and recruitment to treat prostate cancer by flow cytometry and a transwell migration assay