Alternative affinity tools: more attractive than antibodies?

Abstract

Antibodies are the most successful affinity tools used today, in both fundamental and applied research (diagnostics, purification and therapeutics). Nonetheless, antibodies do have their limitations, including high production costs and low stability. Alternative affinity tools based on nucleic acids (aptamers), polypeptides (engineered binding proteins) and inorganic matrices (molecular imprinted polymers) have received considerable attention. A major advantage of these alternatives concerns the efficient (microbial) production and in vitro selection procedures. The latter approach allows for the high-throughput optimization of aptamers and engineered binding proteins, e.g. aiming at enhanced chemical and physical stability. This has resulted in a rapid development of the fields of nucleic acid- and protein-based affinity tools and, although they are certainly not as widely used as antibodies, the number of their applications has steadily increased in recent years. In the present review, we compare the properties of the more conventional antibodies with these innovative affinity tools. Recent advances of affinity tool developments are described, both in a medical setting (e.g. diagnostics, therapeutics and drug delivery) and in several niche areas for which antibodies appear to be less attractive. Furthermore, an outlook is provided on anticipated future developments.

Chromatographic Immunoassays: Strategies and Recent Developments in The Analysis of Drugs and Biological Agents

“…A molecularly imprinted polymer (MIP) is another type of binding agent that can be used as an alternative to antibodies [21][22][23][24][25]. A MIP is a synthetic polymer that is prepared to have recognition sites for a given target.…”

“…A MIP is a synthetic polymer that is prepared to have recognition sites for a given target. This type of material is produced through a polymerization reaction which makes use of one or more functional monomers, a cross-linking agent and a template, with the latter being the target of interest or a compound that is related in structure to the target [21][22][23]. A common scheme for preparing a MIP, or for 'molecular General scheme for a chromatographic immunoassay with direct detection of its target(s) and (B) use of a low-performance 150 mm × 10.0 mm id antibody column for the immunoextraction of d-methamphetamine and related compounds from urine, followed by analysis of these extracted solutes by GC-MS.…”

Perspectives in Glycomics and Lectin Engineering

“…A beneficial feature of such a protein will be high solubility, a small, uniform size of a scaffold protein with an extended chemical and thermal stability and a possibility to express such proteins in prokaryotic expression systems, what is a cost-effective process (81).…”

“…Peptide aptamers are produced by protein engineering from high-complexity combinatorial libraries with appropriate isolation/selection methods (82,80,81). Thus, a need to have knowledge of the protein structure and the mechanism behind binding is not necessary.…”

Label-free affinity biosensor arrays: novel technology for molecular diagnostics

“…A number of comprehensive review articles have been published that focus on biosensor transduction strategies [5][6][7]. There is also a significant body of work on optimized surface chemistries for antibody immobilization and alternative high-affinity binding agents such as antibody fragments, DNA and peptide aptamers, and molecularly imprinted polymers [8]. This editorial provides an overview of two major trends of biosensor research, namely the move towards high-density biosensor arrays and the development of multimodal biosensor technologies.…”