Biology subjects

Ershova, A.

Publications and source records attributed to Ershova, A..

3 recordsLinked to original sources

bioRxiv2026

Enhanced lung delivery of an immunostimulatory duplex RNA augments the antitumor activity by reshaping systemic cytokine pharmacodynamics

The organ-specific enrichment of drug delivery vehicles, such as lipid nanoparticles (LNPs), can be leveraged to concentrate drugs at disease sites to increase efficacy and limit toxicity. For immunostimulatory therapeutics, however, tissue accumulation beyond diseased sites may also shape drug activity by determining which organs and cell populations first sense the agonist and initiate downstream immune responses. Here, we show that the anticancer efficacy of an immunostimulatory duplex RNA (dsRNA) can be augmented using LNPs that are formulated to preferentially target the lung, which dictates the systemic pharmacodynamics of the cytokines it elicits. The immunostimulatory dsRNA was formulated into LNPs engineered for either enhanced liver-(LiverLNPs) or lung-(LungLNPs) based delivery, matched for size, encapsulation efficiency, and in vitro potency. In mice, delivery of dsRNA in LungLNPs enhanced uptake into endothelial, epithelial, and resident immune cells populations and induced substantially higher circulating levels of type I, type III interferons and proinflammatory cytokines than dsRNA formulated in LiverLNPs. This significant systemic response induced by lung-enhanced delivery required competent retinoic acid-inducible gene I and Toll-like receptor 7 signaling. Functionally, LNPs that preferentially targeted the lungs induced significantly greater suppression of tumor growth in both subcutaneous and metastatic models of melanoma. LungLNP/dsRNA also induced cytokine secretion and inhibited tumor cell proliferation in a human lung cancer-on-a-chip model. Together, these results establish that pulmonary exposure can alter systemic pharmacodynamics and therapeutic activity of immunostimulatory RNA.

bioengineering↗

bioRxiv2022

Multi-micron crisscross structures from combinatorially assembled DNA-origami slats

Living systems achieve robust self-assembly across length scales. Meanwhile, nanofabrication strategies such as DNA origami have enabled robust self-assembly of submicron-scale shapes.However, erroneous and missing linkages restrict the number of unique origami that can be practically combined into a single supershape. We introduce crisscross polymerization of DNA-origami slats for strictly seed-dependent growth of custom multi-micron shapes with user-defined nanoscale surface patterning. Using a library of ~2000 strands that can be combinatorially assembled to yield any of ~1e48 distinct DNA origami slats, we realize five-gigadalton structures composed of >1000 uniquely addressable slats, and periodic structures incorporating >10,000 slats. Thus crisscross growth provides a generalizable route for prototyping and scalable production of devices integrating thousands of unique components that each are sophisticated and molecularly precise. One-sentence summaryCrisscross polymerization of DNA-origami slats can yield micron-scale structures with uniquely addressable nanoscale features.

synthetic biology↗

bioRxiv2019

Robust nucleation control via crisscross polymerization of DNA slats

Natural biomolecular assemblies such as actin filaments or microtubules polymerize in a nucleation-limited fashion1,2. The barrier to nucleation arises in part from chelate cooperativity, where stable capture of incoming monomers requires straddling multiple subunits on a filament end3. For programmable self-assembly from building blocks such as synthetic DNA4-23, it is likewise desirable to be able to suppress spontaneous nucleation24-31. However, existing approaches that exploit just a low level of cooperativity can limit spontaneous nucleation only for slow growth, near-equilibrium conditions32. Here we introduce ultracooperative assembly of ribbons densely woven from single-stranded DNA slats. An inbound "crisscross" slat snakes over and under six or more previously captured slats on a growing ribbon end, forming weak but specific half-duplex interactions with each. We demonstrate growth of crisscross ribbons with distinct widths and twists to lengths representing many thousands of slat additions. Strictly seed-initiated extension is attainable over a broad range of temperatures, divalent-cation concentrations, and free-slat concentrations, without unseeded ribbons arising even after a hundred hours to the limit of agarose-gel detection. We envision that crisscross assembly will be broadly enabling for all-or-nothing formation of microstructures with nanoscale features, algorithmic self-assembly, and signal amplification in diagnostic applications requiring extreme sensitivity.

synthetic biology↗