Phage selection strategies

Here, A and I represent the fractions of active and inactive phages, respectively, after (out) or before (in) the selection. A selection strategy is considered efficient if the enrichment factor is higher than 50. 

Immune libraries and evolutionary selection strategies intersect in the area of antibody humanization. Recently, we have extended the repertoire of methods available for the generation of therapeutic human antibodies by developing phage display strategies for the selection and humanization of antibodies from immune animals other than mice. Our aim here was to modify protein sequence, in some cases in a very radical way, and yet retain the function of the parental antibody. In the following discussion, we will focus on these novel approaches. 

As described for antibody humanization, phage display strategies for selecting new antibodies can also be utilized to evolve existing antibodies. 

One advantage of phage display libraries is that selection strategies which employ infection are more likely to be successful, since it seems that more than one functional p3 is required for infection. This has been recently exploited in two model systems. In the first, an antigen is attached to the C terminal of the first two domains of g3p and antibodies are attached to the N terminus of the last domain of g3p [16, 17]. Libraries for this kind of selection need to be specifically prepared. In the second case, an antigen is displayed within the context of the pilus and the antibody is displayed at the N terminus of p3 [18], Selections using these methods are discussed later. 

Antibodies have been displayed Well tested for many proteins Proteins displayed at high levels Infection selections strategies possible Phage or phagemid forms possible... 

Slower to select (helper phage needed) Soluble Ab made directly Phenotypic and genotypic heterogeneity More stable genetically Infection selection strategies unlikely... 

Alternatively, combinatorial phage display strategies have been used as an efficient mean of selecting inorganic binding peptides that promote the rapid, room temperature precipitation of tailored metal oxide particles. Silver binding peptides were thus identified and found to promote synthesis of silver particles... 

Using a similar selection strategy, Lee et al. identified a bacteriophage that had the propensity to bind to ZnS crystal surfaces [116]. These phages were then mixed with ZnS quantum dots, forming a liquid crystalline suspension of the complex. This will push forward the areas of nano-electronic, optical and magnetic sciences and engineering. 

We have previously developed an in vivo selection method in which peptides that home to specific vascular beds are selected after intravenous administration of a phage display random peptide library [5]. This strategy revealed a vascular address system that allows tissue-specific targeting of normal blood vessels [6-8] and angiogenesis-related targeting of tumor blood vessels [3, 6, 9-12]. While the biologi-... 

Griffeths AD, Duncan AR. Strategies for selection of antibodies by phage display. Curr Opin Biotechnol 1998 9 102-108. 

Kretzschmar, T., Zimmermann, C, and Geiser, M (1995) Selection procedures for nonmatured phage antibodies—a quantitative comparison and optimization strategies. A nal Biochem 224,413-419. 

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