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Prologue
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The first candidates for the VLP protein engineering were described in the mid-1980s and included at once the three main structural forms of the experimental VLP candidates. First, the filamentous phage f1 came from the Inoviridae family of the Tubulavirales order covering the rod-shaped phages (Smith 1985), which are described in Chapter 11. This groundbreaking paper paved the way to the enormous field of the phage display methodology. It is special pride of the whole VLP protein engineering field that George Pearson Smith was rewarded with the Nobel Prize 2018 in Chemistry, together with Sir Gregory P. Winter “for the phage display of peptides and antibodies” and Frances H. Arnold “for the directed evolution of enzymes.” As stated by the Nobel Committee, George Smith developed in 1985 an elegant method known as phage display, where a bacteriophage … can be used to evolve new proteins. Gregory Winter used phage display for the directed evolution of antibodies, with the aim of producing new pharmaceuticals. The first one based on this method, adalimumab, was approved in 2002 and is used for rheumatoid arthritis, psoriasis, and inflammatory bowel diseases. Since then, phage display has produced antibodies that can neutralize toxins, counteract autoimmune diseases and cure metastatic cancer.(www.nobelprize.org/prizes/chemistry/2018/press-release/)
Potential of Antibody Therapy for Respiratory Virus Infections
Published in Sunit K. Singh, Human Respiratory Viral Infections, 2014
Tze-Minn Mak, Ruisi Hazel Lin, Yee-Joo Tan
Phage display is the cornerstone of display technologies and is based on the concept of creating libraries of protein fragments presented on the surface of phages, which can then be screened for the fragment of interest. Millions of DNA coding for proteins, peptides, antibodies, or antibody fragments are batch-cloned to produce a protein fused to a phage coat protein (pVIII or pIII), which results in the protein or fragment being displayed on the surface of the phage. This generates a library of up to 1011 clones, which is then screened for interaction with specific targets. Phages that have bound to the target substance of interest are then isolated through washing (removal of unbound phages) and elution. This first round of selected phages can then be amplified via bacterial transformation. The selection can be enriched by regrowing the transformed bacteria, and the phage-bound fragments can be then be analyzed before the mAbs are finally eluted [54]. This cyclical screening process is often referred to as bio-panning and mimics the naturally occurring SHM, thus resulting in antibodies with higher affinity.
High-Throughput Screening for Probe Development
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Kimberly A. Kelly, Fred Reynolds, Kelly R. Kristof
Phage display employs a population of bacteriophage genetically modified to display a library on various phage coat proteins (Fig. 1). Phage display offers a number of important advantages such as rapid and economical biological expansion (rather than more time-consuming chemical resynthesis), vast peptide diversity, a rapid screening process, and the availability of many types of phage clones and libraries (19–21). Another important advantage is that bacteriophage, unlike higher organisms, have only one copy of each gene, so protein expression is not dependent on the interaction of multiple genes. Each gene leads to one protein and each protein has one gene, i.e., genotype equals phenotype. A clone isolated based on phenotypic properties is easy to identify by sequencing the appropriate portion of the phage genome. The genotype equals phenotype phenomenon enables screening in a single well, thereby reducing the amount of starting material (proteins, cells, tissue, etc.) needed for the screen and also allowing the competition of displayed entities against each other.
Could bacteriophages be the answer to the COVID-19 crisis?
Published in Expert Review of Anti-infective Therapy, 2021
Antal Martinecz, Marcin W. Wojewodzic
Phage display, on the other hand, may have a very important function in battling both present and future pandemics. Phage display is a rapid technique to identify antibodies directed against any antigen of interest and, as a result, this technology is already in use for developing therapeutic antibodies. This technology relies on the use of phage libraries to identify the sequences with potential for creating neutralizing antibodies against a virus, which can then be produced using recombinant antibody techniques. This requires DNA information from beta cells isolated from people who already produce the relevant antibodies. Both the European Union and the United States of America have ongoing projects to collect convalescent plasma that includes antibodies that target SARS-CoV-2. However, the effectiveness of antibodies obtained from this plasma has not been sufficiently tested at this point and its use is still controversial. More research into the safety and effectiveness of using antibodies from convalescent plasma is still needed, however, assuming it is effective, phage display techniques could be a safer and more cost-effective way of obtaining sufficient quantities of antibodies than collecting them from COVID-19 survivors. This is because it avoids problems caused by batch effects such as differing quantities of antibodies in different patients, avoids the costs associated with collecting plasma, and allows for easier quality control.
Combining random mutagenesis, structure-guided design and next-generation sequencing to mitigate polyreactivity of an anti-IL-21R antibody
Published in mAbs, 2021
Sharon M. Campbell, Joseph DeBartolo, James R. Apgar, Lydia Mosyak, Virginie McManus, Sonia Beyer, Eric M. Bennett, Matthew Lambert, Orla Cunningham
Phage display remains a workhorse for the generation and optimization of biotherapeutics. It provides a versatile platform to represent in excess of 1010 unique, fully human, synthetic or immune repertoires for panning against conserved proteins, specific epitopes, particular protein conformations or protein complexes.1–4 Additionally, carefully designed selection strategies can drive for cross-species reactivity, homolog specificity and thermal stability.5–7 Conversely, in the absence of the natural in vivo processes of B-cell receptor editing and negative selection, the iterative enrichment that underpins phage display can result in the emergence of poor biophysical properties, such as reduced stability, increased aggregation propensity and nonspecific binding.8–10 Increased net complementarity-determining regions (CDR) loop charge, and the presence of positively charged patches, have been associated with nonspecificity, poor in vivo pharmacokinetics (PK) and ultimately unfavorable developability.8,11–13
Targeting central nervous system pathologies with nanomedicines
Published in Journal of Drug Targeting, 2019
Shoshy Mizrahy, Anna Gutkin, Paolo Decuzzi, Dan Peer
Phage display is an effective molecular technique based on a direct linkage between phage phenotype and its encapsulated genotype, which leads to the presentation of molecule libraries on the phage surface. This technique is being utilised in studying interactions between a protein and its ligand, receptor binding sites, and in improving the affinity between a certain protein to its binding ligand. Phage display is an efficient method for obtaining specific proteins and peptide that can bind to certain receptors, thus provides a key tool for identifying novel agents (e.g. antibodies, proteins or peptide) that can bind the BBB and facilitate the transport between the blood to brain parenchyma in the RMT pathway. Therefore, phage display libraries represent huge potential for formulating targeted drug delivery platforms [136].