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Camelid Antibodies

Sharon Craggs

Jun 25, 2018

Antibody Engineering Recombinant Antibodies

The discovery that camelid produce functional antibodies devoid of light chains has opened the door to many new applications and opportunities. The research applications and therapeutic potential of nanobodies are extremely promising and It will likely become more promising as increasingly efficient methods of producing them continue to evolve.

Author: Sharon Craggs An experienced researcher and technical advisor with laboratory experience in academic and small biotechnology laboratories.

Sharon Craggs

Immunoglobulins are widely used research tools, applicable to a huge diversity of laboratory techniques. We are all familiar with the five primary isotypes found in serum (IgG, IgA, IgM, IgE and IgD). However, the discovery that camelid (camels, llamas and alpacas) produce functional antibodies devoid of light chains has opened the door to many new applications and opportunities.

Structure

Camelid immunoglobulins have a molecular weight of approximately 100kDa, which is considerably lower than a typical IgG immunoglobulin (150kDa). It has been hypothesised that this allows camelid immunoglobulins to target epitopes which are inaccessible to IgGs, such as the catalytic clefts of enzymes. This gives researchers a new and powerful tool with which to investigate proteins that were previously extremely challenging to study. This has, for example, included in research designed to elucidate how neurotransmitters such as adrenaline can bind to receptors in the brain.

Each heavy chain of a camelid immunoglobulin is composed of two constant domains and a single variable domain. The latter is commonly referred to as the VHH domain or nanobody and, despite the lack of light chains, contains a complete antigen binding site, making it the smallest naturally-derived functional antigen binding fragment currently known, with a molecular weight of just 15kDa.

Benefits

The small size of nanobodies means that they offer a wealth of advantages. This includes an exceptional stability in conditions of extreme temperature or pH. This makes them attractive for diagnostic kits such as ELISA or lateral flow assays that do not require refrigeration. Furthermore, they also provides the opportunity for additional routes of administration such as oral immunotherapy. Nanobodies can also penetrate tissues more easily than their larger counterparts and are suitable for target binding within living cells. Further advantage include the possibility of a more rapid accumulation in tissue during imaging studies or therapeutic applications, and potentially lower toxicity due to more rapid clearance. Nanobodies can also be coupled to various detection moieties or solid surfaces. This allows their incorporation into existing protocols in place of traditional IgGs.

While it is possible to produce nanobodies via the typical and well-known route of animal immunisation followed by subsequent purification and characterisation. These valuable reagents can also be readily expressed in bacteria. This ensures a consistent and reliable supply that is virtually limitless. A recent Nature publication has also reported a fully in vitro platform for nanobody discovery based on yeast surface display. Bacterial and yeast-based approaches represent ethical and cost-effective alternatives to animal-based methodologies.

The future of camelids

The range of companies supplying nanobodies for research use is growing steadily. Currently commercially available IgG immunoglobulins currently out-number nanobodies significantly. However, it seems highly likely that nanobodies will experience greatly increased usage in the future. Nanobodies have already been documented within clinical trials and pre-clinical testing for indications including oncology, inflammation, pulmonary disease and neurology, and many further programmes are in developmental phases. The research applications and therapeutic potential of nanobodies are extremely promising. It will likely become more promising as increasingly efficient methods of producing them continue to evolve.

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