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Using viral vectors as gene delivery vehicles for gene therapy necessitates their quality control. Here, we report on nanopore sensing for nondestructively inspecting genomes inside the nanoscale cargoes at the single-molecule level. Using ionic current measurements, we motion-tracked the adeno-associated virus (AAV) vectors as they translocated through a solid-state nanopore. Considering the varying contributions of the electrophoretic forces from the negatively charged internal polynucleotides of different lengths, the nanocargoes carrying longer DNA moved more slowly in the nanochannel. Moreover, ion blockage characteristics revealed their larger volume by up to approximately 3600 nm in proportion to the length of single-stranded DNA packaged inside, thereby allowing electrical discriminations of AAV vectors by the gene-derived physical features. The present findings can be a promising tool for the enhanced quality control of AAV products by enabling the screening of empty and intermediate vectors at the single-particle level.
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http://dx.doi.org/10.1021/acsnano.4c01888 | DOI Listing |
PNAS Nexus
September 2025
Department of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211, USA.
DNA data storage is a promising alternative to conventional storage due to high density, low energy consumption, durability, and ease of replication. While information can be encoded into DNA via synthesis, high costs and the lack of rewriting capability limit its applications beyond archival storage. Emerging "hard drive" strategies seek to encode data onto universal DNA templates without de novo synthesis, using methods such as DNA nanostructures and base modifications.
View Article and Find Full Text PDFResearch (Wash D C)
September 2025
Molecular Sensing and Imaging Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China.
O-glycopeptides are highly expressed in various human cancers and play a key role in cancer progression and metastasis, making them promising biomarkers for early diagnostics. However, the inherent complexity and heterogeneity of glycans pose a major challenge for the simultaneous and precise analysis of multiple glycopeptides. Here, we developed a low-temperature nanopore technique capable of simultaneously discriminating 4 truncated O-glycopeptides with varied glycoforms.
View Article and Find Full Text PDFSmall
September 2025
Faculty of Electrical Engineering, Częstochowa University of Technology, Al. Armii Krajowej 17, Częstochowa, 42-200, Poland.
Bent-core nematic liquid crystals exhibit unique properties, including giant flexoelectricity and polar electro-optic responses, making them ideal for energy conversion and electro-optic applications. When confined in nanopores, they can stabilize chiral nanostructures, enhance polar order, and enable defect-driven switching - offering potential in nanofluidics, sensing, and adaptive optics. The thermotropic ordering of the bent-core dimer CB7CB confined in anodic aluminum oxide (AAO) and silica membranes with precisely engineered cylindrical nanochannels - ranging from just a few nanometers to several hundred nanometers-is examined.
View Article and Find Full Text PDFSolid state nanopores have emerged as powerful tools for single-molecule sensing, yet the rapid uncontrolled translocation of the molecule through the pore remains a key limitation. We have previously demonstrated that an active dual-nanopore system, consisting of two closely spaced pores operated via feedback controlled biasing, shows promise in achieving controlled, slowed-down translocation. Translocation control is achieved via capturing the DNA in a special tug-of-war configuration, whereby opposing electrophoretic forces at each pore are applied to a DNA molecule co-captured at the two pores.
View Article and Find Full Text PDFProtein Sci
August 2025
Department of Chemistry, University of Massachusetts Amherst, Amherst, Massachusetts, USA.
Outer membrane β-barrel proteins (OMPs) are channels found in the outer membranes of Gram-negative bacteria characterized by a stable and diverse barrel architecture, which has made them attractive for nanopore sensing applications. Here, we systematically investigated the feasibility of expanding outer membrane protein G (OmpG) from its native 14-stranded β-barrel to an enhanced conductance variant by independently duplicating each of its seven hairpin units and inserting them downstream of their endogenous positions. Most combinations did not increase pore diameter, but duplication of the terminal seventh hairpin exhibited a rare population of pores with enhanced conductance, suggesting barrel enlargement.
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