Shih, William MDembele, Hawa2026-06-0920262026-05-132026Dembele, Hawa. 2026. Programmable DNA origami nanoparticles as cancer therapeutic vehicles. Doctoral Dissertation, Harvard University Graduate School of Arts and Sciences.32701648https://dash.harvard.edu/handle/1/42740326DNA origami nanoparticles have emerged as a uniquely programmable platform for therapeutic delivery. This thesis explores the development and therapeutic application of DNA origami nanoparticles across three studies that demonstrate the utility of DNA origami nanoparticles as effective cancer immunotherapy platforms.The first study consolidates and validates gel-based and fluorescence-based approaches for the quantitative characterization of protein, peptide, and RNA cargo loading on DNA origami nanoparticles, providing a practical framework for their characterization as therapeutic platforms. The second study investigates the application of a DNA origami-based vaccine platform enabling co-delivery of tumor antigens and CpG adjuvant at precisely defined nanoscale spacing (DoriVac) in metastatic melanoma, demonstrating a significant reduction in metastatic tumor nodules. The third study extends the DoriVac platform to HPV-induced malignancies, demonstrating superior anti-tumor immunity when compared to varying control formulations. Collectively, these studies establish DNA origami nanoparticles as a versatile and effective platform for cancer immunotherapy, with demonstrated preclinical efficacy across two cancer indications and strong potential for clinical translation.application/pdfenCancer VaccineDNA origamiHPVimmuno-oncologyMetastasisnanoparticlesSystematic biologyBioengineeringImmunologyThesis or Dissertation2026-06-09https://orcid.org/0000-0002-5760-875X