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Posted on Jun 25, 2018, 4 p.m.
Nanobodies are therapeutic proteins which are derived from heavy chain domains of IgG of camelids, free of many of the complications and side effects of conventional antibodies.
Conventional antibodies are proteins comprised of 2 heavy chains and 2 light chains, each chain contributing to antigen binding sites, target binding has noncovalently associated variable domains: VL being the light chain component, and VH being for the heavy chain component; with 2 peptide loops at each V-domain tip to mediate target specificity of the molecule.
Camelid IgG antibodies have highly soluble antigen binding V-domain VHH nanobodies, due to size and nanometer range. Nanobodies have hydrophilic sides that correspond to light chains of heavy chain component antibody domains. Nanobodies do not bind light chains and are not complicated by solubility and aggregation problems that occur with heavy chain component domains.
Camelids produce functional antibodies devoid of light chains, cartilaginous fish also produce single domain antibodies, but antibodies from camels are prefered for biotech development as they are easier to handle. Nanobodies carry advantages due to single domain structures, such as libraries created from immunized camelids having full functional diversity, and high affinity antigen binding antibodies can be isolated by screening clones from immune libraries without prior selection using display technologies.
Nanobody single domain structures enable molecular manipulation that can be engineered into multivalent formats to increase affinity or produce bispecific antibodies, which are expected to be more suitable for single cell production of antibody mixtures as they eliminate domain mispairing. They are functional at 90 degrees celsius and have increased stability attributed to hydrophilicity of VL interface regions, increased stability makes them versatile in potential applications. Nanobodies recognize unusual antigenic sites and can be used as enzyme inhibitors.
Oral immunotherapy fields hold great promise for nanobody applications as they are stable at a range of pH levels and can bind targets in the presence of high concentrations of agents that disrupt hydrogen bonds in water. They can be expressed in multivalent formats or enzyme fusions affording a more plug and play approach to development. Nanobodies do not have many of the complications and side effects of conventional antibodies, being produced economically in microorganisms.
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- The development of nanobodies for therapeutic applications.
- Naturally occurring antibodies devoid of light chains.
- Properties, production, and applications of camelid single-domain antibody fragments.
- Isolation of antigen specific llama VHH antibody fragments and their high level secretion by Saccharomyces cerevisiae.
- Comparison of physical chemical properties of llama VHH antibody fragments and mouse monoclonal antibodies.
- Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies.
