Bacteriophages, or phages, are viruses that infect bacteria. Since their discovery in the early 20th century, they have played a crucial role in understanding fundamental biological processes. One of the most transformative applications of bacteriophages in biotechnology is in the field of phage display, a powerful technique for the study of protein-protein interactions and the discovery of therapeutic antibodies.
Bacteriophage Genetics: Laying the Groundwork
The study of bacteriophage genetics has provided many insights into molecular biology, including the understanding of genetic recombination, DNA replication and repair, and gene regulation. The simplicity of phages, coupled with their complex interactions with bacterial hosts, made them ideal models for these studies.
One type of phage, called M13, became particularly important due to its unique life cycle. Unlike many phages, which lyse (break apart) their bacterial hosts, M13 phages are secreted from the bacterium without killing it. This feature has made them attractive tools for genetic engineering and, ultimately, phage display.
The Birth of Phage Display
Phage display was first described in 1985 by George P. Smith. The fundamental idea behind phage display is that a gene encoding a protein (or peptide) of interest is fused to a gene encoding a phage coat protein, resulting in the display of the protein on the surface of the phage.
This was a revolutionary concept because it allowed the physical linkage of genotype (the DNA within the phage) and phenotype (the protein displayed on the phage surface). This meant that millions of proteins could be simultaneously screened for binding to a target, and the genes encoding proteins with the desired binding properties could be easily identified.
Phage Display in Antibody Discovery
The application of phage display for antibody discovery began in earnest in the 1990s. Phage display libraries of antibodies or antibody fragments were developed, enabling the selection of antibodies against a vast array of targets.
Using this technology, antibodies can be selected based on their binding affinity and specificity to virtually any antigen, making it an invaluable tool for therapeutic antibody discovery. Today, several therapeutic antibodies discovered through phage display, such as adalimumab (Humira®) for rheumatoid arthritis, are in clinical use.
The journey from basic research in bacteriophage genetics to the development of therapeutic antibodies through phage display exemplifies the power of investing in fundamental science. The story of phage display underscores the often-unpredictable nature of scientific discovery, where studies on tiny viruses infecting bacteria led to breakthroughs in our ability to combat human disease. As our understanding of bacteriophages continues to grow, no doubt these fascinating organisms will continue to offer new ways to understand and treat disease.