DRUG-seq technology

Unbiased whole transcriptome screening

MERCURIUS™ DRUG-seq is a powerful solution for compound screening and drug discovery, enabling ultra-high-content, unbiased, and high-throughput profiling with extraction-free transcriptomics. The method leverages rigorously optimized sample barcodes and unique molecular identifiers (UMIs) to label the 3' poly(A) tails of mRNA molecules during the first-strand cDNA synthesis. This efficient tagging approach ensures precise sample identification, robust transcript quantification, and seamless scalability for large screening campaigns.

Extraction-free

Skip tedious RNA extraction steps and go straight to library prep.

Cell lysis buffers are highly optimized for 2D cell cultures and organoid models to generate library preps efficiently without prior RNA isolation.

Massive sample multiplexing

Up-to 384 samples processed in one single tube!

Our highly optimized sets of barcoded primers uniquely "tag" individual RNA samples during the first step of library preparation so that you can pool and process all samples together in a single tube early in the workflow.

Pre-amplification-free

Improved protocol for higher mapping and gene detection rates

MERCURIUS™ DRUG-seq leverages a high-yield enzyme for reverse transcription. This streamlines the workflow and eliminates potential biases and duplication introduced with pre-amplification and template-switching oligos (TSO) used in the original DRUG-seq protocol while delivering superior performance.

Benefits

Ideal for screening projects: Massively multiplexed workflow with 96 and 384-well plate formats so that you can screen thousands of samples in parallel at scale.

No need for prior RNA extraction: An optimized lysis buffer ensures complete lysis and efficient reverse transcription to avoid time-consuming and expensive RNA extractions.

Unbiased whole transcriptome screening: No need for prior target selection.

Pre-amplification free protocol: No pre-amplification needed, leading to higher mapping and gene detection rates.

One-day lab workflow: Convenient and quick protocol, from samples to sequencing-ready libraries in one day.

Ultra scalable and ultra low-cost: The more samples processed simultaneously, the lower the cost per sample.

Suited to automation: Enables seamless integration into high-throughput workflows, furter reducing hands-on time and increasing scalability, reproducibility and efficiency.

A scalable and cost-effective transcriptomic profiling solution that accelerates target identification and validation, hit identification, hit-to-lead, and lead optimization.

By providing deep gene expression insights across thousands of compounds, MERCURIUS™ DRUG-seq reveals mechanisms of action, detects on/off-target effects, and uncovers toxicity markers, empowering faster, data-driven decisions throughout the drug development pipeline.

More applications

Mechanism of disease and biomarker discovery

MERCURIUS™ DRUG-seq streamlines ultra-high-content and high-throughput transcriptomic profiling, enabling the rapid and cost-effective identification of disease pathways and key regulatory genes, which can be later used as diagnostic or prognostic biomarkers.

Discover biomarkers faster and with greater confidence to transform data into actionable insights!
Drug resistance

MERCURIUS™ DRUG-seq can also be used to identify drug resistance mechanisms at the transcriptomic level.

This enables researchers to pinpoint molecular adaptations, predict responses, and develop more effective therapeutic strategies.
Toxicology and safety assessment

MERCURIUS™ DRUG-seq is a powerful tool for transcriptome-wide toxicology studies, enabling high-throughput phenotypic screening, cell response screening, and compound activity profiling.

The technology captures comprehensive gene expression changes across thousands of conditions to help identify early toxicity signals, stress responses, and off-target effects. Whether used alone or in combination with CRISPR screens, MERCURIUS™ DRUG-seq provides the resolution and scalability needed to assess compound safety at every stage of drug discovery and to accelerate the development of safer, more effective therapeutics.
AI-driven drug discovery

Artificial intelligence algorithms require vast quantities of robust, in-depth training data for pattern recognition and predictive modeling before researchers can extract meaningful insights with confidence. The unparalleled scalability and cost-effectiveness of MERCURIUS™ DRUG-seq now enables researchers to generate high-throughput transcriptome-wide data for thousands of samples or conditions. These data help to train advanced machine learning models and deep learning algorithms, streamlining screening pipelines and enabling smarter, faster compound discovery.

This integration facilitates scalable phenotypic screening and compound similarity mapping, accelerating mechanism of action identification, target deconvolution, and gene network analysis. Leveraging AI-powered pattern recognition and predictive modeling, researchers can extract meaningful gene signatures and uncover novel biomarkers with greater confidence.

Diverse readout options

3' mRNA sequencing

Focused on sequencing only the 3′ end of mRNA molecules.

Provides a cost-effective and scalable way to measure gene expression levels across thousands of samples.

Targeted mRNA sequencing

Focuses on sequencing specific genes rather than the whole transcriptome.

Increases sensitivity and depth for studying low-abundance transcripts.

Full-length mRNA sequencing

Capture complete transcript information by sequencing the entire length of mRNA molecules, from 5′ to 3′.

This protocol enables comprehensive analysis of transcript isoforms, alternative splicing events, and gene expression levels.

MERCURIUS™

DRUG-seq kit

3' mRNA sequencing
Early multiplexing of up to 384 samples
Directly from cell lysates without prior RNA isolation
12'000 genes detected at 1M reads/sample
Ideal for comprehensive genome-wide gene expression profiling

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MERCURIUS™

Total DRUG-seq

Full-length total RNA sequencing
96 and 384 samples multiplexing format
Directly from cell/organoid lysates without prior RNA isolation
20'000 + genes detected at 10M reads/sample
Full-length RNA transcript coverage: for regulatory RNAs, non-coding RNAs, and early-stage transcripts.

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EARLY-ACCESS

MERCURIUS™

Full-Length

DRUG-seq

Full-length mRNA sequencing
96 samples multiplexing format
Directly from cell/organoid lysates without prior RNA isolation
22'000 genes detected at 12M reads/sample
Full-length mRNA transcript coverage: from differential gene expression to splicing variants and isoform detection

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" We would be glad to work together again"

The DRUG-seq platform enabled us to systematically profile compound-induced transcriptional responses at scale, generating a rich dataset that helped prioritize testable hypotheses. The team at Alithea provided outstanding technical guidance throughout, including support in developing a customized analysis pipeline tailored to our needs. The turnaround time was fast, the process seamless, and the collaboration highly productive. We would be glad to work together again.

Mikołaj Słabicki, Ph.D. Principal Investigator at the MGH Krantz Family Center for Cancer Research. Assistant Professor of Medicine at Harvard Medical School. Affiliate Faculty Member at the Broad Institute of MIT and Harvard

"It's fast, scalable, and incredibly cost-effective"

DRUG-seq has completely transformed how I approach and think about transcriptomic screening. It's fast, scalable, and incredibly cost-effective—perfect for profiling hundreds of compounds in parallel. In my experience, it’s one of the most powerful tools for uncovering mechanisms of action and capturing transcriptional signatures at scale. I've used DRUG-seq to profile different cells treated under time points, dose responses, combination treatments, and a variety of complex cellular models, from cardiomyocytes to organoids—and it consistently delivers high-quality, actionable data. The ability to pool samples early without compromising data quality truly makes it a game-changer.

Andrea Hadjikyriacou, Ph.D. Principal Scientist I, Novartis Biomedical Research

FAQ

MERCURIUS™ DRUG-seq is a transformative tool for compound screening and drug discovery, combining unbiased, ultra-high-content, and high-throughput compound screening with massively parallel and extraction-free transcriptomics. This metho d uses highly optimized and rigorously evaluated sample barcodes and unique molecular identifiers to tag the 3’ poly(A) tail of all mRNA molecules in a sample-specific manner during the first-strand synthesis step of cDNA library preparation.

The DRUG-seq protocol is designed to work with frozen cells and bypass RNA extraction. Thanks to the highly optimized lysis buffers for cell lysis of 2D cell cultures and organoid models, it efficiently generates library preps without prior RNA isolation.
Unlike the original DRUG-seq protocol, which relies on the use of template-switching oligos (TSO) and pre-amplification for the second-strand cDNA synthesis, the MERCURIUS™ DRUG-seq streamlines the workflow by performing the reverse transcription with a high-yield enzyme, thus eliminating the potential biases and duplication introduced with pre-amplification.

This optimized workflow not only simplifies the protocol but also delivers superior performance: higher mapping and gene detection rates.
MERCURIUS™ DRUG-seq stands out from traditional RNA-seq methods by offering a high-throughput, cost-efficient, and streamlined workflow specifically designed for large-scale screening applications. One of the key differences lies in its sample multiplexing strategy: DRUG-seq allows multiple RNA samples to be barcoded and pooled at the earliest step of the protocol—right after cell lysis—so that the entire library preparation can proceed in a single tube. This significantly reduces both hands-on time and reagent costs.

In contrast, standard RNA-seq workflows typically require individual RNA extraction and processing for each sample, followed by separate library preparations. This makes them more labor-intensive, costly, and less scalable, especially when working with large numbers of conditions, compounds, or replicates—common in drug discovery pipelines.
MERCURIUS™ DRUG-seq is used for:

Drug discovery: Identifying new drug candidates and understanding how existing drugs work at a molecular level.

Mechanism of action studies: Understanding how drugs affect cellular pathways and gene regulation.

Drug repurposing: Identifying new uses for existing drugs based on gene expression changes.

Personalized medicine: Tailoring treatments based on individual genetic responses to drugs.

What type of samples can be used in MERCURIUS™ DRUG-seq?

Cell line/Tissue	Organism
HT1080 SMARCA4 KO	Human
hTEC	Human
iPSC microglia	Human
MCF7	Human
HepG2_IGF1RKO	Human
Beas-2B	Human
dTHP-1	Human
iPSC derived cardiomyocytes	Human
Endothelial	Human
Hepatocyte	Human
HEPG2	Human
Hepatocyte	Human
SF9	Spodoptera
A549	Human
Breast Cancer (MCF7)	Human
B lymphoblast MM.1s.	Human
Hek293	Human
HeLa Cells	Human
U2-OS	Human
Hek293	Human
dTHP-1	Human
AsPC-1	Human
PBMC (TCD4)	Human
Skeletal muscle (LHCN-M2)	Human
HepaRG	Human
Macrophage (MV-4-11)	Human
PBMCs (Blood)	Human
Microglia	Human
Fibroblast Like Synoviocyte donor 1502	Human
Fibroblast	Human
iPSC-derived neuron	Human
Human lung carcinoma epithelial cell line	Human
Human breast epithelial adenocarcinoma cell line	Human
Human liver hepatocellular carcinoma cell line	Human
Human cardiomyocytes derived from induced pluripotent stem cells (iPSCs)	Human

DRUG-seq technology

Unbiased whole transcriptome screening

Extraction-free

Massive sample multiplexing

Pre-amplification-free

Benefits

A transformative tool for next-gen drug discovery

Decoding drug responses

Gene detection overview

Enables accurate clustering and co-clustering analysis based on unbiased gene expression measurement

Detect potential synergistic/antagonistic effects of drug combinations

Enables detailed pathway analysis of biological processes

More applications

Mechanism of disease and biomarker discovery

Drug resistance

Toxicology and safety assessment

AI-driven drug discovery

Diverse readout options

3' mRNA sequencing

Targeted mRNA sequencing

Full-length mRNA sequencing

Available as kits and services

Kits for library prep

DRUG-seq kit

Total DRUG-seq

Full-Length

DRUG-seq

Flexible Services

Package 1

Package 2

Package 3

What do our customers say

" We would be glad to work together again"

"It's fast, scalable, and incredibly cost-effective"

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Recent publications

FAQ

What is the difference between Smart-seq2, Smart-seq3, and FLASH-seq for full-length single-cell RNA-seq? 