Chemical Composition and Backbone Modifications Define Deformability of Nucleic Acid Nanoparticles.

ABSTRACT: Nucleic acid nanoparticles (NANPs), composed of short oligonucleotides assembled into specific architectures, are emerging as a programmable platform for the regulated drug delivery of various therapeutic agents. Here, we use a nanopore "clamp" to investigate the mechanical properties of six-stranded RNA and DNA-based NANPs with the connectivity of a cube of sizes below 10 nm. When electrophoretically forced through solid-state nanopores that are smaller than the cubes, deformation of the NANPs generates prolonged electrical signatures whose durations depend on the mechanical deformability of the structures. All-atom MD simulations further reveal differences in the mechanical flexibility of DNA, RNA, modified RNA, and hybrid DNA/RNA cubes, supporting these findings at the molecular level.

SUBMITTER: Pandey L 

PROVIDER: S-EPMC12269358 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature