This technology uses DNA nanoswitches to directly and specifically detect RNA modifications, allowing simultaneous identification of multiple modifications in their natural sequence context for research, diagnostics, and drug discovery applications.
Background: RNA modifications, such as methylation, play critical roles in gene regulation, cellular differentiation, and disease progression, making their detection a priority in molecular biology and biomedical research. The field has rapidly expanded with the discovery that these chemical changes to RNA can influence processes ranging from mRNA stability to translation efficiency. Understanding the distribution and function of RNA modifications is essential for elucidating mechanisms of gene expression regulation and for developing diagnostic and therapeutic strategies for diseases like cancer and neurological disorders. However, the complexity and diversity of RNA modifications, coupled with their occurrence at specific nucleotide positions within transcripts, present significant analytical challenges. Current approaches for detecting RNA modifications have notable limitations. Mass spectrometry, while highly sensitive, requires enzymatic digestion of RNA, which destroys sequence context and prevents mapping modifications to specific sites within transcripts. Sequencing-based methods, such as antibody-based immunoprecipitation followed by high-throughput sequencing, are indirect and often lack single-nucleotide resolution, leading to ambiguous results and potential false positives. Furthermore, these techniques can be labor-intensive, require large amounts of input material, and may not be easily adaptable for multiplexed detection of multiple modifications in a single assay. As a result, there is a pressing need for new technologies that can directly, sensitively, and specifically detect RNA modifications in their native sequence context without sacrificing throughput or accuracy.
Technology Overview: This technology enables the direct and sequence-specific detection of RNA modifications using DNA nanoswitches. A modular design supports multiplexing, enabling simultaneous detection of multiple RNA modifications or quantification of modification levels by generating nanoswitches with distinct loop sizes, all within a single assay. What sets this technology apart is its ability to directly measure RNA modifications in their native sequence context—something that current methods, such as mass spectrometry or sequencing-based approaches, cannot achieve without losing sequence information or requiring complex workflows. This technology provides both high specificity (through sequence hybridization) and high selectivity (through modification recognition), resulting in a versatile and adaptable platform. Its modularity allows researchers to easily modfy the nanoswitches to detect different modifications or combine multiple detectors for multiplexed analysis. This approach not only streamlines the detection process but also opens new avenues for research, diagnostics, and drug discovery by providing a direct, scalable, and user-friendly solution for studying RNA modifications.
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Advantages: • Direct, sequence-specific detection of RNA modifications preserving native sequence context • Supports multiplexing for simultaneous detection of multiple RNA modifications or quantification of modification levels • Modular design for versatile assay configurations • Non-destructive method avoiding RNA digestion or complex sequencing workflows • Applicable to research, diagnostics, drug discovery, and educational settings
Applications: • RNA modification research assays • Clinical diagnostics for RNA biomarkers • Drug discovery screening platforms • Multiplexed RNA modification detection • Educational molecular biology kits
Intellectual Property Summary: Patent application filed
Stage of Development: TRL 4
Licensing Status: This technology is available for licensing.