# Nanopore direct RNA sequencing Reading native RNA molecules strand by strand through a protein nanopore — no reverse transcription, no amplification bias, base modifications visible in the raw current. Two ledger-backed rows; the sequencing-services layer belongs to the sibling page. Source: https://en.bioecon.ru/technology/nanopore-direct-rna-sequencing/ Updated: 2026-09-22 ## Overview and value chain Markers: [EC: RUO boundary for native-RNA transcriptomics; IVD edge marked by GridION Dx CE-IVD/UKCA | OECD: Genomics & bioinformatics | Regulator: FDA (USA), EMA (EU)] Direct RNA sequencing reads an RNA molecule the way it exists in the cell: the native strand passes through a protein nanopore, each base disturbs an ionic current, and the current trace is decoded into sequence. Because the molecule is never reverse-transcribed into cDNA and never amplified, the two distortions that shape most transcriptomics disappear — reverse-transcription bias, which under- and over-represents transcripts, and PCR amplification, which erases the chemical record. That chemical record is the platform's distinctive output: base modifications such as m6A leave characteristic current signatures, so modification mapping runs on the same read that gives the sequence, not on a separate chemistry. The corpus's ledger evidence pairs a chemistry owner with a deployment. Oxford Nanopore owns the platform end: the UK-listed sequencing company (LSE: ONT) runs production at the Harwell Campus in Didcot and the Spectrum facility in Abingdon, builds more than a million flow cells a year, manufactures under ISO 13485, and marks its GridION Dx configuration CE-IVD and UKCA — the regulated edge of a research-first chemistry. Genoscope owns a deployment end: the French national sequencing centre runs nanopores for real-time surveillance of ocean and soil metagenomes, with the nanoMDBG metagenome assembly as its published instrument and the €41.3 million ATLASea program (2024) as its marine-genome mandate. The boundary against sibling pages: long-read-sequencing-services owns the service layer and the PromethION DNA long-read row; spatial-transcriptomics owns measurement geometry; bioinformatics-multi-omics owns the downstream analysis. This page owns the native-RNA chemistry itself. Key directions of nanopore direct RNA sequencing: 1. **Native-RNA chemistry (No Conversion):** the strand is read as RNA, so reverse-transcription bias and amplification distortion never enter the measurement. 2. **Modification-aware reads (Chemistry as Signal):** m6A-class base modifications appear in the raw ionic current, making modification mapping a property of the read rather than a separate assay. 3. **Real-time environmental surveillance (Nanopores in the Field):** Genoscope's ocean and soil metagenome monitoring, assembled through nanoMDBG, runs sequencing as a live instrument rather than a batch service. 4. **Isoform-resolved transcriptomics (Full-Length Reads):** full-length strand reads resolve isoforms directly, with barcode-aware adaptive sampling and an updated cDNA-PCR kit extending the platform's transcriptomic reach. ### Sectoral value chain ``` [native RNA sample] ──> [direct-RNA library prep] ──> [pore flow cell] │ (live basecalling, modifications) ▼ [surveillance / transcriptomics] <── [real-time analysis] <── [current-trace reads] ``` ### Value chain levels | Level | Description | Key inputs/outputs | |:---|:---|:---| | **Native extraction** | intact RNA recovered without degradation | **In:** biological sample. **Out:** full-length RNA. | | **Library preparation** | adapters ligated to native strands | **In:** intact RNA. **Out:** sequencing-ready library. | | **Pore translocation** | strands pass through protein pores | **In:** library. **Out:** ionic-current traces. | | **Live basecalling** | current decoded into sequence and modifications | **In:** current traces. **Out:** modified-sequence reads. | | **Real-time analysis** | assembly and surveillance while sequencing runs | **In:** reads. **Out:** genomes, modification maps, alerts. | | **Deployed insight** | transcriptomics or environmental monitoring | **In:** analysis. **Out:** biological and operational decisions. | Cross-cutting technologies of the sector: - **Adaptive sampling (Selective Reading):** the platform rejects or retains molecules mid-read, steering capacity toward targets of interest. - **Metagenome assembly pipelines (Field-Grade Assembly):** nanoMDBG-class assemblers turn noisy metagenomic reads into usable genomes in surveillance settings. - **Diagnostic device compliance (The IVD Edge):** CE-IVD and UKCA marking on the GridION Dx configuration separates the research chemistry from the regulated diagnostic device. --- ## US The direct-RNA ledger record has no US rows yet, so this section records the structural frame rather than vendor claims. ### Research-use chemistry, the IVD boundary, no US ledger rows - **RUO framing:** native-RNA transcriptomics runs as research-use chemistry; the FDA research/diagnostic boundary is what a clinical claim would have to cross. - **Ledger gap:** no sourced US direct-RNA deployment dossiers exist yet — a screen-wave target. - **Ownership note:** the platform company is UK-listed (LSE: ONT); US market presence is not carried in the ledger evidence. --- ## CN China appears in the ledger evidence as equipment inside a European deployment, not as a direct-RNA ledger row. ### CN platforms in the platform mix, no direct-RNA ledger depth - **MGI DNBSEQ-G400 in the mix:** Genoscope's sequencer fleet pairs Oxford Nanopore pores with Illumina and MGI short-read platforms — a CN-made platform inside the ledgered deployment. - **Ledger gap:** no sourced CN direct-RNA dossiers exist yet — a screen-wave target. --- ## EU Europe carries both ends of the ledgered value chain: the UK chemistry owner and the French national deployment. ### UK production, French surveillance, regulated edge - **Oxford Nanopore (Oxford, UK):** 1,314 employees; production at the Harwell Campus (Didcot) and the Spectrum facility (Abingdon); more than one million flow cells per year; ISO 13485 manufacturing; GridION Dx marked CE-IVD and UKCA. - **Genoscope (Evry-Courcouronnes, France):** the national sequencing centre at the Genopole biocluster; real-time ocean and soil metagenome surveillance on MinION, GridION and PromethION pores; nanoMDBG assembly; €41.3 million ATLASea grant (2024) under CEA, France Génomique and ANR funding; a 1,700-core cluster with 1.5 PB storage. --- ## Leading companies and research institutes | Company / Institute | Country | Key products / platforms | Tech features | Status 2026 | |:---|:---|:---|:---|:---| | **Oxford Nanopore** | 🇬🇧 United Kingdom | *Nanopore direct RNA chemistry; PromethION/MinION/GridION* | 1,314 staff; >1 m flow cells/yr; ISO 13485; GridION Dx CE-IVD/UKCA; adaptive sampling | Commercial | | **Genoscope** | 🇫🇷 France | *Real-time metagenomic surveillance (nanoMDBG)* | MinION/GridION/PromethION fleet; ATLASea €41.3 m; 1,700-core cluster | Research | --- ## Tech stack and innovations The stack runs from one intact RNA sample to one deployed insight — and every stage exists to keep the molecule native. 1. **Native chemistry (Read What Exists):** - the strand is never copied, so the sequence and its modifications arrive in one measurement. - case: Oxford Nanopore's direct-RNA and extended transcriptomic kits on MinION, GridION and PromethION hardware. 2. **Current-level decoding (Signal as Truth):** - base modifications are read from the ionic-current trace itself, not inferred from a converted copy. - case: modification-aware basecalling on the platform's live readout. 3. **Surveillance-grade analysis (Sequencing as Instrument):** - assembly pipelines sized for field conditions turn streams of reads into monitoring output. - case: Genoscope's nanoMDBG metagenome assembly behind its ocean and soil programs. --- ## Value chains and production pipelines ### Industrial pipeline of a direct-RNA sequencing campaign (native-molecule regime) ``` ┌───────────────────────────┐ ┌───────────────────────────┐ │ 1. Sample to native RNA │ ───> │ 2. Library preparation │ └───────────────────────────┘ └───────────────────────────┘ │ ▼ ┌───────────────────────────┐ ┌───────────────────────────┐ │ 4. Live basecalling │ <─── │ 3. Pore flow cell │ └───────────────────────────┘ └───────────────────────────┘ │ ▼ ┌───────────────────────────┐ ┌───────────────────────────┐ │ 5. Real-time analysis │ ───> │ 6. Deployed insight │ └───────────────────────────┘ └───────────────────────────┘ ``` #### Stage 1: Sample to native RNA Intact, full-length RNA is recovered from the biological sample without amplification. #### Stage 2: Library preparation Adapters are ligated to native strands; an updated cDNA-PCR kit extends the route where RNA input is limited. #### Stage 3: Pore flow cell The library loads onto a flow cell; strands translocate through protein pores one molecule at a time. Production capacity exceeds one million flow cells per year at the Harwell plant. #### Stage 4: Live basecalling Ionic-current traces decode into sequence and modification calls as the read passes — barcode-aware adaptive sampling steers the run mid-flight. #### Stage 5: Real-time analysis Assembly and surveillance pipelines process reads while the run continues; nanoMDBG-class assembly supports environmental monitoring. #### Stage 6: Deployed insight Transcriptomes, modification maps and surveillance signals become operational output — research findings or environmental alerts.