Phage Display

The phage display technology is a valuable approach in the biomedical field that offers a rapid, efficient and inexpensive tool for detecting protein-protein interactions, investigating receptor binding sites, identifying epitopes, mimotopes as well as functional sites of antigens. Due to its high flexibility, this technique has become an attractive target for scientists and methods based on phage display are allowed to explore the mechanisms of diseases, improve diagnostic capability and design potential agents for therapeutics.

Phage display is a completely random manner. In Creative Biolabs, we are able to construct large repertoires of antibodies (10⁹-10¹²), which are displayed on the surface of filamentous phages, and from which peptides or proteins with desired properties can be screened for the development of drugs, vaccines, and reagents. Finally they are decoded by sequencing of phage DNA.

Phage Display Methodology at Creative Biolabs

▶ Library technology features:

• ✔ Large functional size with high antibody sequence diversity, facilitating the selection of various high-affinity antibodies;
• ✔ Antibody genes are well expressed, allowing the automation of panning processes and the amplification of expression levels for production purpose;
• ✔ Library design requires the rapid engineering of antibodies for optimizing lead candidates, and the immunogenicity of the antibodies is low for therapeutic uses;
• ✔ The overall handling of the library is simple and convenient to allow cooperation with any species.

Fig.1 Schematic presentation of antibody fragments. (Bazan, 2012)

• Peptide Library

  -- Random phage peptide library is one of the most common types in phage display designs. Introducing degraded oligonucleotides into the phage genome will enable the realization of a linear random peptide library, which permits screening of ligands for targets.

• Recombinant Antibody Library

  -- By using phage display technology, we have generated recombinant antibodies with high specificity for any antigen. Several forms of recombinant antibody fragments have been designed to be used in the phage display selection, including Fab fragments, scFab fragments, scFabΔC fragments, and so on (Fig.1).

• Immunized Antibody Library

  -- We can also provide immunized human antibody libraries with the highest affinity, stability, and specificity. The library capacity is up to 10⁹-10¹⁶. The immunized antibody libraries, including scFv, Fab, VHH types, will build a valuable foundation for immunotherapy and contribute to the improvement of drug development.

▶ Biopanning

Creative Biolabs has constructed both large non-immune and synthetic libraries as well as smaller immune libraries based on capturing a single immune repertoire. Our phage display platforms represent advanced methodology for high-throughput screening for therapeutic antibody candidates of interest. Initially, phage display library is incubated with targets immobilized on solid scaffolds. Specific library phages bind to target molecules, while the unbound phages are washed away. Then specific phages are eluted and amplified by infecting E. coli cells. After several rounds of selection, amplified clones can be sequenced and analyzed to obtain diagnostic and therapeutic agents with wanted properties.

Fig.3 Phage display selection. (Frei, 2016)

Except for traditional biopannings, we are also pleased to introduce many other specific selection strategies.

• Phage Display Library Screening by Subtractive Selection
• Phage Display Library Selection of Antibodies Based on Valency
• Phage Display Library Screening Based on Antibody Kinetic Binding Properties
• Phage Display Library Screening by Epitope Masking
• Phage Display Library Screening by Capture Lift
• Guided Selection for Human Antibody Identification from Non-human Donor
• Antibody-guided Selection using Capture-sandwich ELISA

Area of expertise and services

• ✔ Phage display in transfusion medicine
• ✔ Diagnostic and therapeutic agents for autoimmune diseases
• ✔ Phage display in neurological disorders
• ✔ Tissue homing and anti-angiogenic strategies
• ✔ Molecular imaging and tumor targeting

Phage display is a robust technology for selection of high-quality human antibodies from different libraries. In addition to being able to recognize antibodies in a fast, high-throughput mode, this tool is currently being used to identify fully human therapeutic antibodies according to market-approved regulatory procedures.

If you’re interested in our phage display services or other multifunctional platforms, please contact us for more details.

References

1. Bazan, J.; et al. Phage display -- a powerful technique for immunotherapy: 1. Introduction and potential of therapeutic applications. Hum Vaccin Immunother. 2012, 8(12): 1817-1828.
2. Frei, J.C.; Lai, J.R. Protein and antibody engineering by phage display. Methods Enzymol. 2016, 580: 45-87.
3. Omidfar, K.; Daneshpour, M. Advances in phage display technology for drug discovery. Expert Opin Drug Discov. 2015, 10(6): 651-669.