Biology subjects

Dobrovolskaia, M. A.

Publications and source records attributed to Dobrovolskaia, M. A..

2 recordsLinked to original sources

bioRxiv2022

Artificial immune cell, AI-cell, a new tool to predict interferon production by peripheral blood monocytes in response to nucleic acid nanoparticles

Nucleic acid nanoparticles, or NANPs, are rationally designed to communicate with the human immune system and can offer innovative therapeutic strategies to overcome the limitations of traditional nucleic acid therapies. Each set of NANPs is unique in their architectural parameters and physicochemical properties, which together with the type of delivery vehicles determine the kind and the magnitude of their immune response. Currently, there are no predictive tools that would reliably guide NANPs design to the desired immunological outcome, a step crucial for the success of personalized therapies. Through a systematic approach investigating physicochemical and immunological profiles of a comprehensive panel of various NANPs, our research team has developed a computational model based on the transformer architecture able to predict the immune activities of NANPs via construction of so-called artificial immune cell, or AI-cell. The AI-cell will aid addressing in timely manner the current critical public health challenges related to overdose and safety criteria of nucleic acid therapies and promote the development of novel biomedical tools.

bioinformatics↗

bioRxiv2022

Innate Immune Stimulation using 3D Wireframe DNA Origami

3D wireframe DNA origami have programmable structural and sequence features that render them potentially suitable for prophylactic and therapeutic applications. However, their innate immunological properties, which stem from parameters including geometric shape and CpG content, remain largely unknown. Here, we investigate the immunostimulatory properties of 3D wireframe DNA origami on the TLR9 pathway using both reporter cell lines and primary immune cells. Our results suggest that bare 3D polyhedral wireframe DNA origami induce minimal TLR9 activation despite the presence of numerous internal CpG dinucleotides. However, when displaying multivalent CpG-containing ssDNA oligos, wireframe DNA origami induce robust TLR9 pathway activation, along with enhancement of downstream immune response as evidenced by increases in Type I and Type III IFN production in peripheral blood mononuclear cells. Further, we find that CpG copy number and spatial organization each contribute to the magnitude of TLR9 signaling, and that NANP-attached CpGs do not require phosphorothioate stabilization to elicit signaling. These results suggest key design parameters for wireframe DNA origami that can be programmed to modulate immune pathway activation controllably for prophylactic and therapeutic applications.

bioengineering↗