Custom Cell Line Development

Tailored to Your Specific Cell Assay Needs for GPCRs and Beyond

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Custom Cell Line Development to Accelerate Drug Discover

Stable cell lines play a pivotal role throughout the drug discovery process, from target validation to lead candidate selection for IND. Their significance spans a diverse array of druggable proteins, such as GPCRs, kinases, NHRs, transporters, integrins, and ion channels. Recognizing this vital role, we provide tailored cell line development to meet specific in vitro assay requirements for each program. This complements our extensive array of optimized MULTISCREEN™ stable cell lines, enhancing the efficiency of the drug discovery journey.

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GPCR custom cell lines, used for HTS screening and drug discovery, image

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With our uniquely combined assay development and cell sciences expertise, the Multispan team can generate custom stable cell lines that meet your projects’ needs. These custom-generated MULTISCREEN™ stable cell lines are highly characterized single-cell clones, selected and validated in functional assays, and ready to go in high throughput screening and compound profiling. Due to the clonal nature of MULTISCREEN™ stable cell lines, these cell lines guarantee a high performance that will withstand the test of time. 

Tailored Solutions in Custom Cell Line Development for Target Validation and HTS

  • Collaborative consultation to strategize your screening funnel
  • Isolation and cloning of the specific target cDNA variant
  • Development of stable cell lines for G-protein or beta-arrestin assays using MULTISCREEN™ GPCR assay kits
  • Direct clone selection through diverse modalities: full/partial agonist, antagonist, PAM, or NAM
  • HTS screening assay optimization tailored to a 384-well format
  • Comprehensive scaling, banking, and validation of cell lines
  • Delivery of a “3-in-1” turnkey solution with cells, assay kits, and validated protocols
  • Option to leverage Multispan for direct compound screening, minimizing assay transfer time and costs
Custom Cell Line Development Workflow

Custom Cell Line Development for Secondary HTS Assays and Profiling

To ensure comprehensive secondary counter screens and robust compound profiling in the critical stages of hit-to-lead, lead optimization, and candidate selection, we specialize in custom cell line development. This extends to both primary cells and our recombinant MULTISCREENTM stable cell lines, precisely tailored to the targets of interest. Our services cover a wide spectrum of functional and translational assays.

  • Signaling Biases: Integration of GPCR assays such as Beta-arrestin, Calcium, cAMP, IP-1, pGRK2, and pERK
  • Translational Readout: Encompassing insulin secretion, cytokine secretion, chemotaxis, and pNF-κB.
  • Target Engagement: Employing techniques like radioligand binding, GTPγ-S, and internalization.
  • Translational Assay: Developing both wild-type and mutant stable cell lines with endogenous targets modulated by siRNA and CRISPR
  • Ortholog Cross-Reactivity: Covering species such as rodents, dogs, and non-human primates
  • Off-Targets: Profiling of target variants and other related family isotypes
  • Cell line management: Scaling, banking, and validating cell lines for stability, expression and function
  • Turnkey Solutions: “3-in-1” delivery: MULTISCREENTM cell line, assay kit, and validated assay protocol
  • Rapid Screening: Choose compound screening at Multispan, boasting a 1-day turnaround for SAR campaigns

Distinctive Benefits of Custom-Generated MULTISCREENTM Stable Cell Lines for Enhanced Research Outcomes

  • Integrated Approach: Cell line generation seamlessly aligned with functional assay creation optimized for HTS needs
  • Target Diversity: Encompasses a broad spectrum from GPCRs, kinases, NHRs, transporters, integrins, and ion-channels
  • Expression Versatility: Produces stable cell lines with both endogenous and heterologous expression
  • Comparative Analysis: Ensures uniform pharmacology and expression between human and ortholog targets
  • Isogenic Pairs: Features both wild-type and knockout mutants of endogenously-expressed targets
  • Collaborative Selection: Single clones chosen based on relevant functional readouts, emphasizing early customer input
  • Stringent Validation: Custom-developed MULTISCREENTM stable cell lines undergo rigorous MULTISCREENTM quality control process to validate sequence, growth, expression, function, contamination and stability
  • Prompt Delivery: Custom cell line development designed for a swift turnaround to shorten research timeline

Tailoring Cell Line Development by Choosing the Right Parental Cell Line

MULTISCREENTM cell line development integrates Multispan team’s cell engineering, assay development, and HTS experience and expertise to succeed. Two main categories of cell lines are routinely deployed and engineered by the Multispan team for cell assays.  They are either primary cells expressing the endogenous protein target or stable cell lines that have very low or no expression of endogenous protein target. The isogenic pair of custom MULTISCREENTM stable cell lines from the parental cells are engineered by deploying various techniques such as CRISPR knock-in and knock-out, and heterologous recombination target expression. 

To serve the purpose of robust potency assays, we have developed a broad spectrum HTS assays using primary cells such as hepatocytes, hiPSC derived microglial cells, human ventricle interstitial cardiomyocytes (hVIC), primary fibroblasts, PBMC, and mouse islet cells. In the case of heterologous recombination custom stable cell line, we employ Multispan’s highly characterized MULTISCREENTMstable cell lines, designed, generated, and QC’ed for high throughput screening assays. These potency assays are either driven by target-induced cell signaling or translational biological events such as cell proliferation.

Tailoring Cell Line Development by Choosing the Right Assay Readout

MULTISCREENTM Readouts Used in Custom Cell Line Development

At Multispan, we are dedicated to advancing cell line and assay development, and our commitment extends to selecting the most appropriate readouts for specific research needs. Our expertise spans a range of assay types, including ELISA, cell-based ELISA, reporter assays, binding assays, 2nd messenger assays, flow cytometry (FACS) in readouts like fluorescence, chemiluminescence assays, TR-FRET assays, absorbance assays, and even radioisotope-based assays.

We understand that the choice of readout is crucial in accurately measuring the biological events and mode of action in your research. This precision and customization allows us to offer tailored solutions to meet the unique requirements and contribute to the success of each project in the drug discovery and biotechnological endeavor.

Tailoring Cell Line Development by Choosing the Right Assay Mode of Action

At Multispan, our approach to cell line development is intricately tied to the biology of each target and the specific mechanism of therapeutic intervention. We recognize that a one-size-fits-all approach simply won’t suffice. Thus, we employ different assay modalities for High-Throughput Screening (HTS), ensuring that the custom-developed cell lines are meticulously tailored to meet the screening requirements.

These modalities encompass a spectrum of modes, including agonist, partial agonist, antagonist, partial antagonist, inverse agonist, positive allosteric modulator (PAM), and negative allosteric modulator (NAM) modes. Each mode is selected with precision, aligning with the unique biology of the target and the intended therapeutic outcome.

Our commitment to excellence also extends to the careful selection of tool compounds used for each cell line development. These compounds are chosen to reflect the specific mode of action, ensuring that our assays are not only highly effective but also aligned with the intricate details of the research objectives of each program.

As we strive for the perfect clone in each custom cell line development project, we prioritize transparency, updating our clients on progress and welcoming feedback at every stage.

With a track record spanning over nearly two decades, our 100% delivery rate stands testament to our dedication. At the core of our efforts lies an unwavering commitment to customer satisfaction

Resources:

Article: GPCR Stable Cell Lines

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