Application of phage display (Part 2)-Special Topic on Phage Display Technology-Tekbiotech-Yeast and Phage Display CRO, Expert in Nano-body and Antibody Drug Development

Application of phage display (Part 2)

Application 3: Discovery of Peptide Drugs and Lead Compounds

PhagePro Tech? is the preferred platform for peptide discovery for the following reasons. First, phage libraries boast an ultra-large capacity, easily generating peptide libraries containing 10? to 1011 distinct sequences. Second, surface-displayed amino acid sequences of phages correspond one-to-one with inserted DNA fragments, enabling direct sequencing and large-scale production. Third, in vitro screening is free from interference by physiological conditions and fully controllable. Fourth, customized functional screening protocols can be established. Peptide libraries are categorized by structure into linear peptide libraries, cyclic peptide libraries and transmembrane peptide libraries.

① Identification of Cell-Penetrating Peptides

Specific cell lines (e.g., tumor cells, stem cells) are incubated with phage libraries under physiological conditions. Internalized phages are released via treatments such as trypsin digestion, cultured and subjected to subsequent rounds of incubation. This strategy enables screening of phages that spontaneously penetrate cells without prior knowledge of their receptors or action mechanisms. Notably, phages merely bound to the cell surface must be distinguished from truly internalized ones to ensure recovery of intracellular phages.

Screening can isolate peptides that specifically penetrate target cells such as cancer cells while barely penetrating normal cells. Unbound phages remaining outside normal cells are collected and incubated with target cells to recover phages with target cell binding and internalization capacity. The resulting cell-penetrating peptides exhibit superior selectivity toward target cells and serve as valuable tools for targeted drug delivery.

② Tissue-Specific Delivery Peptides

Screening is performed under complex in vivo physiological conditions. Phage libraries are injected into model animals such as mice via tail vein for systemic circulation. After a designated period, target tissues are harvested. Multiple rounds of screening enrich phages capable of homing to target tissues and crossing vascular and cellular barriers. Phages obtained through this workflow possess tissue-targeting properties and act as core tools for targeted drug development.

Application 4: Gene Therapy and Cell Therapy

① Gene Therapy

Conventional gene therapy vectors (adenoviruses, lentiviruses) mainly target human cells. In contrast, phage-based gene therapy modifies commensal bacteria residing in the intestinal tract or other human niches by delivering therapeutic genes into symbiotic bacteria to treat human diseases indirectly.

For instance, phages can deliver genes encoding anti-inflammatory cytokines (e.g., IL-10) to intestinal flora. Engineered gut bacteria continuously secrete anti-inflammatory agents locally to modulate intestinal immune homeostasis. This approach avoids side effects induced by systemic administration, featuring enhanced safety and sustained drug release.

② Cell Therapy

PhagePro Tech? plays an indispensable role in cell therapy, especially CAR-T and TCR-T therapy. Phage libraries are screened to isolate specific antibodies such as single-chain variable fragments (scFv), which constitute the core targeting moieties of CAR-T cells for tumor-specific therapy. Phage-derived TCR libraries support identification of TCRs that recognize tumor-specific MHC-peptide complexes.

Phage display applications-1.png

Figure 1

Application 5: Development of Diagnostic Reagents

1. Pathogen Capture Assay

Phage libraries undergo iterative screening against target bacteria. Specific phages are immobilized on detection platforms; signal shifts occur once phages capture target bacteria, enabling real-time detection. Compared with monoclonal antibodies, phage probes feature higher stability and simpler mass production.

2. Diagnostic Method Based on Phage Lysis

Samples are incubated with target-specific phages. If viable target bacteria exist in samples, phages infect and lyse host bacteria, releasing intracellular substances. Signals such as ATP, reporter genes and secreted enzymes can be measured for pathogen identification.

Schematic Diagram of Phage-Based Pathogen Detection Principles-2.png

Figure 2: Schematic Diagram of Phage-Based Pathogen Detection Principles

Tek Biotechnology (Tianjin) Co., Ltd. has built a comprehensive targeted antibody drug discovery platform based on phage display technology. The company provides high-quality VHH neutralizing monoclonal antibody development services for researchers worldwide, covering preliminary development and validation of therapeutic monoclonal antibodies against GPCR targets, tumor targets and various disease-related targets. One-stop technical services are offered, ranging from project design to druggability evaluation, to meet diverse demands for monoclonal antibody development.

References

[1] Mishra AK,Ali A,Dutta S, et al. Emerging Trends in Immunotherapy for Cancer. Diseases. 2022;10

[2] Yan J,Guo Z,Xie J. A Critical Analysis of the Opportunities and Challenges of Phage Application in Seafood Quality Control. Foods. 2024;13 (20):.

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