Nature Nanotechnology: “Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination.”
This pivotal publication reveals the importance of precise nanospacing control of cargo on nanoparticle vaccines for optimization of immune response and cancer vaccine efficacy. We reported the development and in vitro and in vivo evaluation of the square block DNA origami vaccine (DoriVac). DoriVac elicits robust Th1 immunity and is protective against tumor growth in animal models
This paper evaluated DoriVac as a candidate vaccine to induce immune responses against viral antigens. The data show that DoriVac immunization drives robust T cell responses in addition to high titer antibody responses against several viral targets and sets the stage for a next-generation vaccine targeting pathogens.
Small Methods: "Cargo quantification of functionalized DNA origami for therapeutic application"
In this paper, our study consolidates several previously validated methods focusing on gel-based and fluorescence-based techniques, including multiplexed quantification of protein, peptide, and nucleic acid cargo on these nanoparticles. This work may serve as a valuable resource for groups of researchers keen on utilizing DNA origami-based nanoparticles in therapeutic applications.
BioRxiv: " Reusing excess staple oligonucleotides for economical production of DNA origami"
In this paper, the folding of DNA origami with staple strands that were reused up to eleven times was indistinguishable by our panel of assays versus a control folded with new strands, so long as the reused oligonucleotides were replenished each cycle with a small excess of fresh strands. We also observed a high degree of incorporation of guests on the DNA origami. By recovering, reusing, and replenishing excess staple oligonucleotides, it is possible to significantly lessen production costs to create well-formed origami, which is useful to allow more therapeutic designs to be tested in the lab.
BioRxiv: "Validation of DoriVac (DNA origami vaccine) efficacy in a metastatic melanoma model"
In this study, we observed a significant reduction in lung tumor nodules for mice treated with DoriVac in both the B16OVA and B16F10 metastatic melanoma mouse models. DoriVac also appears to be a safe and effective treatment, with no anti-drug antibodies, as indicated by lower anti-dsDNA levels. Importantly, we observed an amplified effect when DoriVac was combined with αPD-L1 immune checkpoint blockade, leading to an even greater reduction in metastatic lung tumor nodules. Our results also indicate an increased activation of antigen-presenting cells, NK cells, CD4+ T cells, and CD8+ T cells. These findings suggest that DoriVac, particularly in combination with the αPD-L1 immune checkpoint blockade, can serve as a promising immunotherapy against metastatic cancer.
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