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Functional Target Screening by Phage Display

Introduction Services Platforms Highlights FAQs Resources Related Sections

Introduction

In the world of drug discovery and biologics development, binding is only the first chapter of the story. A molecule can bind with incredible affinity and still do absolutely nothing. It might be a neutral binder, or it might bind to a non-functional epitope. This leads to countless dead-end candidates, wasted resources, and frustrating delays. What if your very first screening step isolated candidates based on their actual biological function? This is precisely what we offer at Creative Biolabs. Our functional phage display screening approach is designed to identify ligands (peptides, antibodies, scaffolds) that work, and our multi-platform phage display approach includes in vitro protein-based, in vitro cell-based, ex vivo, and in vivo screening. We run phage display with a single focus on measurable biological function; therefore, we do not end at affinity. We enrich clones that change signaling, shift cell behavior, inhibit enzyme activity, drive apoptosis or senescence, promote lineage commitment, enable organ targeting, or reverse drug resistance. Every decision in our workflow aligns with your outcome, so the readouts you care about stay in control of the selection pressure.

Who This Service Fits?

The schematic of a scientist working in a lab. (Creative Biolabs Authorized)

  • Biotech and pharma R&D programs that need functional modulators for oncology, immunology, neurology, infectious disease, or regenerative medicine.
  • Translational and discovery groups building mechanisms with effect-driven ligands or tool antibodies.
  • Targeted delivery teams seeking tissue-homing ligands, BBB-penetrant binders, vascular addresses, or internalizing receptor binders.
  • Biomarker teams requiring high-specificity ligands with clean functional profiles.
  • Platform owners integrating functional ligands into ADCs, bispecifics, targeted nanoparticles, gene delivery systems, or cell therapies.

Eight Applications Built for Functional Target Screening

Phage Display Screening for Agonists and Antagonists

The discovery of novel agonists and antagonists for cell surface receptors, such as G protein-coupled receptors (GPCRs) or ion channels, is a cornerstone of modern medicine. However, finding these modulators is notoriously difficult. These receptors have complex structures and activation mechanisms that are often lost when the protein is purified. Our approach is different. We perform panning directly on living cells that are engineered to report on receptor activation.

  • Agonist Screening: We isolate phages that trigger the reporter signal on their own.
  • Antagonist Screening: We first add a known agonist to initiate the signal, then introduce the phage library to find clones that inhibit or block that signal.

Discovery of Enzyme Inhibitors by Phage Display

Enzymes are the workhorses of the cell, and their dysregulation is linked to countless diseases, from metabolic disorders to cancer. Finding specific, potent inhibitors is a primary goal for many therapeutic programs. Traditional high-throughput screening (HTS) of small molecule libraries can be effective, but it often misses opportunities, especially for complex allosteric sites or protein-protein interaction (PPI) blocking. Phage display, particularly of peptide and VHH libraries, offers a powerful alternative. Creative Biolabs has developed a suite of functional screening strategies to isolate potent enzyme inhibitors:

  • Substrate-Mimetic Screening: We can design panning rounds where the phage must compete with a labeled substrate for binding to the enzyme's active site.
  • Activity-Based Panning: In a more sophisticated setup, we immobilize the enzyme and incubate it with the phage library in the presence of its substrate. We then specifically elute the phage that successfully prevented the substrate from being converted to a product.
  • Allosteric Site Discovery: Our methods are not limited to the active site. By panning against the full enzyme, we can identify molecules that bind to novel allosteric sites and modulate activity, offering new avenues for drug design with potentially higher specificity and fewer side effects.

Antibody Screening with In Vivo Phage Display

This is the ultimate functional screen. Screening in vitro on plastic plates or even on cultured cells can never fully replicate the complexity of a living organism. The tumor microenvironment, the blood-brain barrier (BBB), and the complex interplay of the immune system—these factors are missing. In vivo phage display screening bridges this gap. By administering a phage library systemically into a relevant animal model, we allow the selection pressure to be applied by the organism itself. After circulation, we harvest the target organ, recover the phage, and amplify it for the next round of panning. The result is a pool of antibody candidates that are proven to reach and engage your target in the most relevant physiological context possible.

Screening for Tumor Apoptosis & Senescence Targets

Forcing a cancer cell to die (apoptosis) or stop dividing (senescence) is a core goal of oncology. But which targets on the cell surface, when activated, will trigger these self-destruct pathways? Identifying these functional targets is a massive challenge. Creative Biolabs uses a phenotypic screening approach that directly selects for this outcome. We identify ligands that induce apoptosis or establish senescence in tumor models, including therapy-resistant backgrounds. We frequently uncover novel targets and pathways that were previously overlooked, opening up entirely new therapeutic strategies.

Discovering Novel Anti-Angiogenesis & Anti-Metastasis Targets

A tumor cannot grow beyond a tiny size without a blood supply (angiogenesis), and the vast majority of cancer mortality is due to its spread (metastasis). Targeting these two processes is a proven strategy. But the current drugs are not universally effective, and resistance often develops. We urgently need new targets. Creative Biolabs uses functional, cell-based assays to screen for phage-displayed molecules that physically stop these processes. Our offerings include:

  • Anti-Angiogenesis Screening: We use assays that model the formation of new blood vessels, such as the endothelial cell tube formation assay. We pan our libraries for phages that, when added to the culture, inhibit the endothelial cells from forming these capillary-like structures.
  • Anti-Metastasis Screening: We use cell migration and invasion assays. We apply the phage library and select for clones that prevent the cancer cells from migrating across the membrane.

Finding Novel Immune Checkpoint Modulators

Finding the next generation of immune checkpoint modulators requires accurate functional screening. Our platform is ready to screen both known targets (like PD-1, CTLA-4, LAG-3, TIGIT) and novel checkpoints in either human or murine systems. We go far beyond simple binding. Whether your program needs an antagonist to block a pathway or an agonist to activate one, we can find it. We also support your downstream development with species-matched counters and options for advanced bispecific or Fc-engineered formats.

Discovering Stem Cell Differentiation & Tissue Regeneration

Controlling stem cell fate is the ultimate goal of regenerative medicine. Our functional phage display screens are designed to find the exact molecules that guide this process. We work directly with your specific stem cell or organoid systems—spanning neuronal, cardiac, hepatic, and mesenchymal models. Our advantage is our comprehensive validation: we combine marker expression, morphology, and actual functional readouts to find hits that actually drive lineage commitment or tissue regeneration. We adapt our screening design, including scaffold-free or matrix-aware approaches, to your specific biological model to ensure physiologically relevant results.

Screening for Drug Resistance Reversal Targets

Drug resistance is a critical clinical hurdle. Our functional screens are designed to find molecules that restore sensitivity to your chemotherapy or antibiotic. The key to our success is screening under active drug pressure. This robust method specifically isolates true "re-sensitizers" that disrupt resistance mechanisms, such as efflux pumps or alternative survival pathways. We deliver fully-ranked candidates based on their rescue magnitude and selectivity. This provides you with a clear, actionable plan for combination studies and moves your program forward immediately.

Phage Display Screening Platforms at Creative Biolabs

Fig.1 Creative Biolabs offers four phage display screening platforms, including in vitro protein-based phage display screening, in vitro cell-based phage display screening, ex vivo phage display screening, and in vivo phage display screening. (Creative Biolabs Original)Fig.1 Four phage display screening platforms at Creative Biolabs.1

Our Phage Display Screening Platforms scale biological complexity in alignment with your program's risk profile and decision milestones—many campaigns utilize multiple platforms to compress uncertainty while maintaining speed.

Why Creative Biolabs

  • Function-first, we optimize for the biological effect your program needs.
  • We offer an unparalleled collection of proprietary phage display libraries, including peptide, scFv, VHH, and Fab libraries. We can also custom-build a library just for your project.
  • A comprehensive service suite is available here: we support reformatting, optimization, and mechanism studies.
  • Experience across many areas as part of our daily work, including oncology, immunology, neurological delivery, antimicrobial resistance, and regenerative biology programs.

Provide the biological objective, species, and format needs, any known target or structural constraints, available counter-targets or control lines, timeline or capacity considerations, and downstream goals such as ADC, bispecific, fusion protein, or delivery conjugation. This context allows us to configure selection pressure and QC to your real decision points. If you are ready to shift selection pressure toward the outcomes that move your program forward, we will configure a function-first screen and a platform sequence that fits your objectives and capacity. Send your goals, constraints, and timelines; we will return a clear plan and an execution schedule. If you want to start a project, please feel free to contact Creative Biolabs and get your tailored solutions.

FAQs

Can you run a function-linked selection if the readout is complex?

Yes. We design selections around reporter systems, imaging-based quantification, kinetic enzyme assays, uptake/internalization, or co-culture effects. When a direct in-round readout is impractical, we interleave biochemical rounds with short functional confirmation cycles to keep enrichment aligned with the endpoint.

Do I need a defined target to use functional phage display?

No. Many projects start with a phenotype-first objective, such as apoptosis induction, pathway activation, or drug resistance reversal. After functional hits emerge, we can perform target deconvolution or binding partner identification to support mechanism and translational planning.

What ligand formats can you deliver at the end of the screen?

We can hand off enriched phage clones, peptide sequences, or antibody fragments. Upon request, we reformat to IgG, Fc-fusions, or multivalent constructs and provide developability checkpoints such as expression level, aggregation, and stability.

Can you combine platforms in one program?

Yes. A typical pattern is protein-based pre-screening to remove obvious liabilities, followed by cell-based selection for native conformation, then ex vivo to confirm tissue selectivity, and finally in vivo for biodistribution. This staged approach compresses risk without slowing progress.

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