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DriverMap™ Cell-Free Assays

Cell-Free RNA and DNA Profiling for Biomarker Discovery in Liquid Biopsy

Cellecta's DriverMap™ Cell-Free Profiling Assays turn a standard blood draw into an informative source of potentially therapeutic and diagnostic biomarkers. The method co-purifies cell-free RNA (cfRNA) and cell-free DNA (cfDNA) from human plasma, then uses targeted multiplex PCR and next-generation sequencing (NGS) to profile three biomarker classes from the same sample:

  • immune receptor repertoires,
  • gene expression signatures and
  • cancer-associated viruses.

These assays allow researchers to discover biomarkers and track them over time with a minimally-invasive screening approach.

  • Cells throughout the body release cell-free DNA and RNA into the bloodstream. cfDNA—fragmented DNA that primarily comes from apoptosis and necrosis of blood or tumor cells—shows which cells are dying. cfRNA—packed into extracellular vesicles (EVs) and exosomes or present in the soluble plasma fraction—shows which genes are active in the cells that release it. This minimally-invasive plasma profiling technique can provide information from tumors, immune cells, organs, and virus-infected cells that a blood-based assay cannot provide.

    Most liquid biopsy tests on the market today read only tumor mutations in cfDNA. DriverMap™ Cell-Free Profiling Assays read both cfRNA and cfDNA and focus on biology that mutation-tracking does not allow.

    • Get the off-the-shelf kits to run the complete workflow in your lab, requiring only standard equipment and Illumina sequencing instruments, or
    • Get the end-to-end service workflow, wherein you send in samples and receive back a comprehensive report in a few weeks.

    DriverMap™ Cell-Free RNA & DNA Purification Kit
    Optimized magnetic bead technology co-purifies cfRNA and cfDNA from 1–6 mL of plasma in one prep. It recovers the degraded nucleic acids in EVs, exosomes and the soluble fraction, and gives one eluate that is an input for all DriverMap™ cell-free profiling assays.

    DriverMap™ Cell-Free AIR TCR/BCR RNA & DNA Profiling Kit
    Profiles the CDR3 region of all seven TCR and BCR chains (TRA, TRB, TRG, TRD, IGH, IGK, IGL) from 10–1,000 ng of cell-free nucleic acid (cfNA) in a single-day workflow. Two barcoded hybridization reactions separate the cfRNA signal (lymphocyte activation) from the cfDNA signal (lymphocyte turnover) in one library prep.

    DriverMap™ Cell-Free EXP 5K Profiling Kit (Available soon)
    Profiles the expression of about 5,000 human genes in plasma cfRNA. The targeted panel filters out the abundant background of housekeeping RNAs derived from platelets, which gives at least a 100-fold increase in sensitivity compared with RNA-seq, for disease- and tissue-specific transcripts.

    DriverMap™ Cell-Free OncoVirus Detection Kit (Available soon)
    Detects 26 viral sequences associated with cancer development in both cfRNA and cfDNA from the same plasma sample.

    This workflow requires 3 separate products

    1. DriverMap™ Cell-Free RNA & DNA Purification Kit (Optional: Other commercially available purifications kits may be used)
    2. DriverMap™ Cell-Free Profiling Kits (Required)
    3. Universal UDI NGS Plate (Set A, B, C or D) (Required)

    DriverMap Cell-Free Assays for liquid-biopsy biomarker discovery

    Fig. 1. DriverMap™ Cell-Free Assays for liquid-biopsy biomarker discovery. The Cell-Free RNA & DNA Purification Kit co-purifies both fractions in one prep. Targeted multiplex PCR-NGS assays then profiles immune receptor repertoires, gene expression signatures and oncoviral sequences.

  • How does the DriverMap™ Cell-Free Profiling Assay work?

    1. Collect blood and prepare plasma. Collect blood in EDTA tubes and process plasma the same day. Freeze 1–5 mL plasma aliquots at –80 °C.
    2. Co-purify cfRNA and cfDNA with the DriverMap™ Cell-Free RNA & DNA Purification Kit
    3. Run the DriverMap™ Cell-Free Assay for your biomarkers of interest adaptive immune repertoire (AIR), gene expression (EXP 5K) or oncovirus detection (26- virus panel). Each assay produces targeted multiplex RT-PCR, Illumina –compatible NGS libraries, ready for sequencing.
    4. Sequence and analyze. Sequence the libraries on an Illumina instrument, then -quantify the results. Use recommended software for quantifying analysis of FASTQ files, and Cellecta also offers additional downstream data analysis services.

  • How are DriverMap™ Cell-Free Assays Different from Other Available Cell-Free Assays?

    • RNA and DNA from One Prep
      The purification kit keeps both fractions in one eluate. cfRNA reports gene activity and cfDNA reports cell death, so from one sample you obtain two layers of information.
    • Beyond Tumor Mutations
      Profile immune responses, tissue-of-origin expression and viral activity — biomarker classes that mutation-based cfDNA tests do not cover.
    • Sensitivity for Low-Input Samples
      Optimized targeted multiplex PCR-based assays detect templates present at very low copy numbers in plasma. The DriverMap cfAIR assay profiles 10-100 CDR3 sequences; the DriverMap cfEXP 5K assay is at least 100-fold more sensitive than RNA-seq.
    • Simple, In-House Workflow
      Off-the-shelf kits, requiring only standard lab equipment and Illumina sequencers. No specialized instruments are needed.

  • Some Applications

    • Cancer Immunotherapy Monitoring
      Track tumor-reactive TCR and BCR clonotypes in plasma before and during checkpoint-inhibitor therapy, without a new biopsy.1,10
    • Lymphoid Malignancies
      Detect and follow malignant B-cell and T-cell clones in plasma cfDNA and cfRNA.2,3
    • Disease Biomarkers for Pre-term Pregnancy & Endometriosis
      Use cfRNA expression signatures to predict or monitor diseases such as pregnancy complications or uterine diseases.6
    • Virus-Associated Cancers
      Screen for and monitor EBV-, HPV- and other virus-associated cancers through sensitive detection of viral DNA and RNA in plasma.7,8,9

  • Key Publications

    Immune receptor profiling in cell-free plasma

    1. Soleimani S, et al. T cell receptor repertoire in cell-free DNA as a proxy for tumor infiltrates in patients treated with pembrolizumab. Cell Rep. 2025. PubMed 40875293
    2. Albitar A, et al. Using cell-free RNA to identify B- and T-cell clonality for diagnosis and monitoring of B- and T-cell neoplasms. FEBS Open Bio. doi:10.1002/2211-5463.70323

    Gene expression profiling in plasma cfRNA

    1. Larson MH, et al. A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection. Nat Commun. 2021;12:2357. doi:10.1038/s41467-021-22444-1
    2. Vorperian SK, et al. Cell types of origin of the cell-free transcriptome. Nat Biotechnol. 2022;40:855–861. doi:10.1038/s41587-021-01188-9
    3. Moufarrej MN, et al. Early prediction of preeclampsia in pregnancy with cell-free RNA. Nature. 2022;602:689–694. doi:10.1038/s41586-022-04410-z

    Oncoviral profiling in cell-free plasma

    1. Chan KCA, et al. Analysis of plasma Epstein–Barr virus DNA to screen for nasopharyngeal cancer. N Engl J Med. 2017;377:513–522. doi:10.1056/NEJMoa1701717
    2. Chera BS, et al. Rapid clearance profile of plasma circulating tumor HPV type 16 DNA during chemoradiotherapy correlates with disease control in HPV-associated oropharyngeal cancer. Clin Cancer Res. 2019;25(15):4682–4690. doi:10.1158/1078-0432.CCR-19-0211
    3. Chera BS, et al. Plasma circulating tumor HPV DNA for the surveillance of cancer recurrence in HPV-associated oropharyngeal cancer. J Clin Oncol. 2020;38(10):1050–1058. doi:10.1200/JCO.19.02444

    Cellecta data

    1. Chenchik A, Paraiso K, Hyder K, Diehl P, Ghias K. Immune repertoire sequencing of cell-free DNA/RNA from plasma and extracellular vesicles for minimally invasive testing. Cellecta poster, 2026. PDF