Publications by authors named "Andrew J Sinegra"
Cancer vaccines must activate multiple immune cell types to be effective against aggressive tumours. Here we report the impact of the structural presentation of two antigenic peptides on immune responses at the transcriptomic, cellular and organismal levels. We used spherical nucleic acid (SNA) nanoparticles to investigate how the spatial distribution and placement of two antigen classes affect antigen processing, cytokine production and the induction of memory.
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- Lipid nanoparticle SNAs (LNP-SNAs) are designed to effectively deliver DNA and RNA to cell cytoplasm, with their activity influenced by both the lipid core composition and the DNA sequences on their surface.
- G-rich DNA sequences and higher cholesterol content in the LNP core enhance the effectiveness of these nanoparticles, allowing for significant reductions in the amount of siRNA needed to silence mRNA.
- The distribution of LNP-SNAs varies based on their structure, showing that mRNA from these nanoparticles primarily localizes to the spleen, whereas standard LNPs without surface DNA tend to accumulate more in the liver, indicating potential for targeted tissue delivery.
Spherical nucleic acids (SNAs) are a class of nanomaterials with a structure defined by a radial distribution of densely packed, short DNA or RNA sequences around a nanoparticle core. This structure allows SNAs to rapidly enter mammalian cells, protects the displayed oligonucleotides from nuclease degradation, and enables co-delivery of other drug cargoes. Here, we investigate the biodistribution of liposomal spherical nucleic acid (LSNA) conjugates, SNA architectures formed from liposome templates and DNA modified with hydrophobic end groups (tails).
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