Abstract

Antibody discovery has become increasingly important in almost all areas of modern medicine. Different antibody discovery approaches exist, but one that has gained increasing interest in the field of toxinology and antivenom research is phage display technology. In this review, the lifecycle of the M13 phage and the basics of phage display technology are presented together with important factors influencing the success rates of phage display experiments. Moreover, the pros and cons of different antigen display methods and the use of naïve versus immunized phage display antibody libraries is discussed, and selected examples from the field of antivenom research are highlighted. This review thus provides in-depth knowledge on the principles and use of phage display technology with a special focus on discovery of antibodies that target animal toxins.

Highlights

  • With the recent inclusion of snakebite envenoming on the World Health Organization’s list of Neglected Tropical Diseases [1], focus on both prevention and treatment of this infliction has increased

  • One approach is phage display selection [10], which is a robust, easy-to-perform, and inexpensive method by which specific antigen binders are selected from large combinatorial libraries containing billions of antibody fragments

  • As antibody phage display is gaining increasing interest in the field of toxinology, the intention with this review is to provide both basic and more advanced knowledge on the underlying science behind the technology and the lifecycle of the M13 phage

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Summary

Introduction

With the recent inclusion of snakebite envenoming on the World Health Organization’s list of Neglected Tropical Diseases [1], focus on both prevention and treatment of this infliction has increased. One promising approach seems to be the use of human IgG antibodies [6] and/or camelid antibody fragments [7,8], as these molecules can be used to develop recombinant antivenoms with high efficacy and safety due to their compatibility with the human immune system [2]. These therapeutic proteins could be manufactured cost-competitively using modern cell cultivation methods employed for large scale production [6,9]. As antibody phage display is gaining increasing interest in the field of toxinology, the intention with this review is to provide both basic and more advanced knowledge on the underlying science behind the technology and the lifecycle of the M13 phage

The M13 Bacteriophage
Coat protein Assembly
Using the M13 Phage as a Tool in Antibody Discovery
Phage and Phagemid Libraries
Phagemid Libraries Are Amplified Using Helper Phages
Gene product fromhelper helperphage phageand andgene gene III-scFv
A After sisi nn ftertryp tryp
Performing a Phage Display Selection Experiment
Antigen Quality and Presentation
10. Closing Remarks
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