World's first RNome sequencing platform

Uncovering Ground-Truth Sequences with All Modifications.

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About Us

DirectSeq technology services fills a crucial quality assurance gap for RNA therapeutics developers, and delivers on the true RNome for the first time, providing the first unbiased, comprehensive and exhaustive means by which to directly sequence and confirm the identity of all RNA species present in a sample.

With a foundation in advanced mass spectrometry and molecular biology, we're pushing the boundaries of scientific discovery to unlock the full complexity of RNA molecules including their sequence, structure, and modifications all in a single experiment.

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The Problem

Regulatory scrutiny of RNA therapeutics is intensifying as modified ribonucleotide bases—essential for drug function and stability—can also introduce unintended, toxic, or persistent contaminants.

Existing analytical methods like PCR or LC-MS cannot detect or quantify these base-level modifications, leaving critical safety gaps in therapeutic validation and regulatory compliance.

DirectSeq uniquely solves this challenge by providing true de-novo RNA sequencing capable of identifying both intended and unintended nucleotide modifications with unmatched precision.

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DirectSeq Technologies

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Direct and Exhaustive RNA Sequencing

Our DSMX™-Seq platform directly sequences RNA molecules without cDNA conversion, ensuring 100% accuracy and complete retention of base modification data. It captures every RNA species in a sample from major transcripts to minor isomers in a single, comprehensive run.

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De-Novo Sequencing of All RNA Species

Unlike LC-MS or reference-dependent methods, DSMX™-Seq determines RNA identity through de-novo base-calling from mass differences. This approach enables empirical, bias-free identification of all RNA molecules and modifications.

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Unprecedented Detection of Modified Bases

Our 3D DSMX™-Seq technology can identify all 170+ known ribonucleotide modifications, even when clustered on the same RNA strand. It quantifies both canonical and modified bases, revealing complex RNA isoforms down to < 1% abundance.

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Revolutionizing RNA Therapeutic Quality Control

DSMX™-Seq empowers RNA therapeutic developers with the ability to detect, sequence, and quantify minor RNA variants that contribute to off-target effects. It sets a new benchmark for RNA quality assurance and lot-to-lot consistency.

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DirectSeq Solutions & Offering

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Expanding DSMX-seq™ Adoption

Our present focus is to expand adoption of our DSMX-seq™ platform among RNA therapeutics professionals and RNome investigators, empowering labs to achieve deeper transcriptomic insights.

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Comprehensive & Unbiased RNA Sequencing

As the only platform capable of unbiased, comprehensive, and exhaustive discernment of all RNA species present in a sample—including contaminants containing modified ribonucleotide bases—DSMX-seq™ sets a new standard for RNA analytics.

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Solving RNA Therapeutics Challenges

We offer a solution that addresses several critical problems that currently hinder developers of small RNA, vaccine, and monogenic replacement therapies—enhancing confidence in quality, efficacy, and safety.

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Quality Assurance for RNA Therapeutics

Unbiased measurement of sequence purity/diversity and modifications within a sample without prior knowledge of sequences. Essential for sgRNAs, siRNAs, and other RNA therapeutic development and validation.

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Fundamental Biology

Reveal the true nature of RNAs within cells and tissues through comprehensive sequencing and modification analysis, enabling breakthrough discoveries in RNA biology and cellular function.

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Biomarker Discovery for Diagnostics

Leverage differential frequency of specific RNAs and RNA modifications for clinical diagnosis, enabling the development of precise biomarkers for disease detection and monitoring.

Our Team

Leadership Team

Portrait of Shenglong Zhang

Dr. Shenglong Zhang

Founder & President

Leading strategic vision and company growth.

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Portrait of Sam Ruta

Sam Ruta

VP of Sales & Marketing

Driving market expansion and customer relationships.

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Portrait of Tony Frudakis

Dr. Tony Frudakis

Chief Executive Officer

Pioneering leader in genomics and standards for RNA therapeutics quality.

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Lab Team

Portrait of Shangsi Lin

Shangsi Lin

Leader in Bioinformatics

Specializing in RNA sequencing and modification analysis.

Portrait of Dr. Jung Yeon Lee

Dr. Jung Yeon Lee

Leader in LC-MS sequencing data acquisition

Developing algorithms for RNA data analysis.

Portrait of Dr. Justin C. Dingman

Dr. Justin C. Dingman

Leader in RNA sample preparation

Supporting laboratory operations and data collection.

Our Partners

We collaborate with leading academic institutions and research organizations to advance RNA sequencing technology and accelerate discoveries in genomics and precision medicine.

Through strategic collaborations with these esteemed institutions, we combine expertise, resources, and technologies to tackle the most complex challenges in RNA analysis and develop solutions that benefit the entire scientific community.

DirectSeq Publications

Mass Spectrometry-Based Direct Sequencing of tRNAs De Novo and Quantitative Mapping of Multiple RNA Modifications

Journal: Journal of the American Chemical Society • Year: 2024

  • Introduces MLC-Seq, a mass-spectrometry ladder complementation method for direct, cDNA-free sequencing of full-length tRNAs.
  • Simultaneously identifies multiple nucleotide modifications with single-nucleotide resolution and quantitative accuracy.
  • Detects minor isoforms and modification stoichiometry changes, revealing dynamic RNA modification patterns.
  • Enables complete primary sequence and modification context, surpassing conventional LC-MS and sequencing methods.
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Direct de novo sequencing of therapeutic RNA and impurities via layer-by-layer intensity-resolved mass spectrometry

Under Review

  • 3D NGMS-Seq is a next-generation mass-spectrometry-based sequencing platform that enables de novo direct sequencing of mixed RNA samples with 100% accuracy, addressing the growing need for comprehensive RNA analysis in therapeutic development.
  • It enhances conventional LC-MS/MS by integrating MS intensity into 2D mass-retention-time (tR) data, forming a 3D mass-intensity-tR matrix and using a nested alignment algorithm to computationally separate ladder fragments according to parent RNA abundances.
  • Through controlled acid hydrolysis, the method generates ladder fragments, performs base-calling from mass differences to identify canonical and modified nucleotides, and then assembles full-length RNA sequences via statistical modeling and hydrolysis kinetics.
  • Demonstrated on synthetic siRNA, miRNA, and CRISPR/Cas9 sgRNAs, 3D NGMS-Seq uncovered unexpected low-abundance RNA impurities and subtle methylation ambiguities (e.g., Um vs mU; Am vs mA), offering a powerful new tool for RNA drug development, QC, and regulatory validation.
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