Geometry-dependent mRNA delivery with programmable RNA-DNA nanostructures
- 1University of Illinois at Urbana-Champaign
Abstract
Efficient intracellular delivery of neoantigen-encoded mRNAs is central to the development of effective cancer vaccines and immunotherapies. However, how the nanoscale geometry of delivery carriers impacts mRNA delivery remains poorly understood, largely because conventional delivery platforms do not readily permit systematic variation of carrier architecture while maintaining comparable chemical composition. Here, we develop a modular RNA-DNA hybrid nanoplatform that enables controlled investigation of geometry-dependent mRNA delivery. Guided by a unified design principle, we construct a series of two- and three-dimensional nanostructures with programmable architectures and systematically compare their delivery performance using consistent functional readouts. We further investigate how mRNA embedding strategies and aptamer-mediated functionalization influence intracellular delivery efficiency. By providing precise control over carrier geometry, this platform establishes a framework for elucidating structure-function relationships in mRNA delivery and offers a versatile strategy for engineering targeted nucleic acid delivery systems.
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BibTeX
@misc{zheng2026geometrydependent,
title = {{Geometry-dependent mRNA delivery with programmable RNA-DNA nanostructures}},
author = {M. Zheng and A. Dwivedy and D. Gandavadi and W. Hong and H. Cho and N. Shkolnik and X. Wang},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.19.752892},
url = {https://www.biorxiv.org/content/10.64898/2026.09.19.752892v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Geometry-dependent mRNA delivery with programmable RNA-DNA nanostructures
AU - M. Zheng
AU - A. Dwivedy
AU - D. Gandavadi
AU - W. Hong
AU - H. Cho
AU - N. Shkolnik
AU - X. Wang
PY - 2026
DA - 2026/09/19
PB - bioRxiv
DO - 10.64898/2026.09.19.752892
UR - https://www.biorxiv.org/content/10.64898/2026.09.19.752892v1
AB - Efficient intracellular delivery of neoantigen-encoded mRNAs is central to the development of effective cancer vaccines and immunotherapies. However, how the nanoscale geometry of delivery carriers impacts mRNA delivery remains poorly understood, largely because conventional delivery platforms do not readily permit systematic variation of carrier architecture while maintaining comparable chemical composition. Here, we develop a modular RNA-DNA hybrid nanoplatform that enables controlled investigation of geometry-dependent mRNA delivery. Guided by a unified design principle, we construct a series of two- and three-dimensional nanostructures with programmable architectures and systematically compare their delivery performance using consistent functional readouts. We further investigate how mRNA embedding strategies and aptamer-mediated functionalization influence intracellular delivery efficiency. By providing precise control over carrier geometry, this platform establishes a framework for elucidating structure-function relationships in mRNA delivery and offers a versatile strategy for engineering targeted nucleic acid delivery systems.
ER -