DRUG DEVELOPMENT

Precision all
along the drug
discovery pipeline

Use single-cell sequencing in drug development to generate a high-resolution view of your mechanism of action. We support biomarker discovery, mechanism of action analysis, efficacy, and off-target effect studies with the highest-quality single-cell data.

Single-cell sequencing in drug development, Single Cell Discoveries
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Drug discovery pipeline

Single-Cell Sequencing in Drug Development: Mechanism of Disease & Biomarker Discovery

Mechanism of Disease & Biomarker Discovery

Single-Cell Sequencing in Drug Development: Target Identification

Target Identification

Single-Cell Sequencing in Drug Development: Target Validation & Mechanism of Action

Target Validation & Mechanism of Action

Single-Cell Sequencing in Drug Development: Lead Identification & Optimization

Lead Identification & Optimization

Single-Cell Sequencing in Preclinical Research

Preclinical

Single-Cell Sequencing in Clinical Trials

Clinical Trials

Mechanism of disease & biomarker discovery

How single-cell sequencing can
uncover mechanism of disease & identify biomarkers

  • Single-cell transcriptomics reveals distinct cell populations, lineage trajectories, and differentiation states, offering insight into mechanisms of pathogenesis. Analysis of differential gene expression profiles in diseased cells can further uncover dysregulated pathways and key regulatory genes.
  • By comparing diseased versus healthy or responder versus non-responder states, differentially expressed genes and cell-type markers can be discovered and used as diagnostic or prognostic biomarkers.

Single Cell Discoveries solutions for successful mechanism of disease & biomarker discovery

  • Single-cell RNA sequencing through 10x Genomics Single Cell Gene Expression is suited for high-throughput experiments, whereas plate-based SORT-seq or VASA-seq can detect lowly expressed biomarkers and focus on FACS-sorted populations. In addition, full-length single-cell RNA sequencing (VASA-seq) is especially powerful for diseases involving non-coding RNAs, cell cycle defects, and splicing variants.
  • Bulk RNA-seq can inform follow-up single-cell experiments by uncovering biomarker candidates and disease mechanisms of cell populations.
  • 10x Genomics Immune Profiling reveals the immune system's response to pathogens or auto-antigenic stimulation by profiling B and T cell receptors.
  • Spatial transcriptomics is suited to investigate cell-cell interactions and spatially restricted biomarkers.

Target identification

How single-cell sequencing can identify therapeutic targets

  • Comparing the single-cell transcriptomes of diseased and healthy states can reveal disease-associated cell populations, differentially expressed genes, co-expression patterns, and patient subtypes to investigate as drug targets.
  • Single-cell CRISPR screens are a transformative functional genomics approach to perturb thousands of genomic loci in individual cells simultaneously. With our single-cell technologies, we can analyze the transcriptomic responses in your pooled CRISPR screen samples for therapeutic effects.

Single Cell Discoveries solutions for successful target identification

  • Our 10x Genomics Single Cell Gene Expression is ideal for large-scale screens requiring high-throughput analysis of many genetic perturbations or diseased samples. After performing your CRISPR screen, we can analyze the transcriptomic responses to the genetic perturbations.
  • Combine Immune Profiling with barcode-enabled antigen mapping (BEAM) and discover therapeutically desirable, antigen-specific B-cell and T-cell clonotypes. That is useful for antibody discovery, cancer immunotherapy development, and vaccine immunogenicity assays.
  • For studying lowly expressed genetic pathways or FACS-sorted populations, SORT-seq and VASA-seq are ideal. In addition, VASA-seq analysis measures fragments from full transcripts, making it suited for investigating splice sites.
  • Bulk RNA-seq is also compatible with FACS-sorting and can be used to find potential targets differentially expressed over a population of cells. Then, follow-up single-cell experiments can determine target-gene distribution at single-cell resolution.

Target validation & mechanism of action

How single-cell sequencing can validate targets and reveal the mechanism of action of therapeutic candidates

  • Comparing disease versus healthy and responder versus non-responder populations can elucidate the mechanism of therapeutic action.
  • Single-cell transcriptomics data from patients expressing the target can reveal disease-associated cell populations, differentially expressed genes, co-expression patterns, and patient subtypes that validate the mechanism of target-drug interaction.

Single Cell Discoveries solutions for successful target validation and mechanism-of-action determination

  • 10x Genomics Gene Expression is suited for higher-throughput single-cell transcriptomics analysis, whereas SORT-seq may be favored for read depth and FACS-sorted populations.
  • VASA-seq analysis measures fragments from full transcripts, making it ideal for investigating splicing manipulation as a potential therapeutic mechanism. In addition, VASA-seq measures non-polyadenylated RNAs revealing the drug's effect on the cell cycle (via replication-dependent canonical histone mRNAs).
  • 10x Genomics Immune Profiling is transformative for understanding immune system response to therapeutics. Hence, combine Immune Profiling with barcode-enabled antigen mapping (BEAM) and discover therapeutically desirable, antigen-specific B-cell and T-cell clonotypes. That is useful for antibody discovery, cancer immunotherapy development, and vaccine immunogenicity assays.
  • Spatial transcriptomics can uncover drug effects on intercellular communication and microenvironment as well as relating the distribution of target gene expression to drug localization.
Single Cell Drug Development eBook

Single-Cell in Drug Development eBook

From biomarker discovery to clinical trials: how are scientists applying single-cell sequencing to the drug development pipeline? We have reviewed and highlighted seminal studies from the past ten years for your inspiration.

DOWNLOAD

Lead identification & optimization

How single-cell sequencing can identify and optimize lead candidates

  • Single-cell CRISPR screens can reveal genes involved in T cell exhaustion, proliferation, and survival that can be knocked out or knocked in to optimize cell therapies. Similarly, comparing CAR constructs by single-cell sequencing highlights co-stimulatory molecules or domain modifications associated with proliferative or exhaustive signatures.
  • Single-cell sequencing informs immunotherapeutic development by resolving immune responses to different CAR constructs, Fc receptors, or other variable features of a drug candidate.
  • Single-cell sequencing measures transgene incorporation revealing the optimal distribution vehicle and preventing off-target effects.

Single Cell Discoveries solutions for successful identification and optimization of lead candidates

  • 10x Genomics Single Cell Gene Expression is ideal for large-scale screens requiring high-throughput analysis of many candidate therapeutics. Furthermore, 10x Genomics Immune Profiling can further resolve the elicited immune response, revealing the optimal payload. In addition, multiplexing samples with 10x Genomics allows analyzing up to 128 samples at a time. 10x Genomics is also ideal for gene therapy biodistribution studies, revealing the optimal delivery vehicle.
  • Bulk RNA-seq is a lower-cost method for hit identification screening and pairs well with subsequent single-cell sequencing for hit optimization.
  • Spatial Transcriptomics is suited for studying tumor infiltration, biodistribution, and off-target effects.

Preclinical

How single-cell sequencing can evaluate safety, efficacy, and ideal manufacturing conditions

  • Single-cell sequencing can be used to compare the transcriptome between model organisms and patient samples to select the preclinical model with the most translational potential.
  • Single-cell sequencing unveils off-target effects, including incorrect genomic integration or promiscuous activity.
  • Single-cell sequencing in drug development elucidates how cell culture conditions, media formulation, bioreactor, or other manufacturing parameters influence drug product transcriptomes. Transcriptional heterogeneity within batches can further be linked to functional outcomes to reveal optimal signatures.

Single Cell Discoveries solutions for successful determination of safety, efficacy, and ideal manufacturing conditions

  • 10x Genomics is ideal for gene therapy biodistribution studies, enabling delivery vehicle optimization.
  • Profiling of immune features with 10x Genomics Single Cell Immune Profiling can be used to test the efficacy of therapeutic antibodies, track immunogenicity across vaccine strategies, and study the immunotoxic effects of drugs.

Clinical trials

How single-cell sequencing can be used to stratify patients and monitor their responses

  • Single-cell sequencing on patient leukapheresis material linked to patient response reveals transcriptomic signatures, which can be used as prognostic biomarkers to stratify patients.
  • Comparing the single-cell transcriptomic profiles of infusion products and cell products recovered from patients can define signatures of infusion products that are proliferative and persistent in patients.

Single Cell Discoveries solutions for successful monitoring of patient response

  • 10x Genomics Single Cell Gene Expression Flex enables highly sensitive profiling of up to a million formaldehyde-fixed or FFPE tissue, ideal for biopsy or patient-derived xenograft material. It has a scalable workflow that can be run on a flexible schedule, allowing sample storage without quality loss and empowering larger and more longitudinal patient cohort studies. This makes Flex specifically suitable for single-cell sequencing in clinical trials.

Case studies

Pioneering 10x Flex on OCT-Embedded Patient Brain Tissue

10x Genomics opened the gates for single-cell sequencing on non-fresh, non-thawed tissue with their Chromium Single Cell Gene Expression Flex (10x Flex) kit. Now, we have been successful in performing…

10x
Neuroscience
Neuroscience
RNA Flex
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