Nanobody Applications

Applications of Nanobodies

Nanobodies have a number of interesting applications, and many of them are early stages of development. These include basic research to clinical therapeutics. Some of these applications include the following:

Affinity capture reagents

Nanobodies have a larger binding surface and lower nonspecific background binding due to their small size and single domain format. As they bind in a monovalent manner, they can be eluted under mild conditions, and their high stability allows repeated use.

Crystallization chaperones

Nanobodies have been used to chaperone protein crystallization due to their ability to lock proteins in a particular conformation, stabilize flexible domains, and shield aggregating surfaces from solvents. They have been used in a number of protein crystallization studies, and same properties have also been exploited to stabilize amyloid-β protofibrils and prevent formation of mature amyloid fibrils.

Target imaging and immunomodulation

Nanobodies can be expressed inside cells fused with a fluorescent protein to track the activity of their antigen. They can also be used to functionally knock out the antigen in the cell, and fused with signal peptides to be targeted to specific subcellular compartments.

Biosensors

Nanobodies can be adapted for use in biosensors in the fields of medicine, environment, and food analysis. Their site-specific functional groups are easy to introduce and their small size allows for a high capacity binding surface, leading to higher sensitivity.

In vivo imaging

Nanobodies can be used as a tracer for noninvasive molecular imaging to study disease processes. Their small size allows for rapid tissue penetration and blood clearance.

Antivenom therapy

Polyclonal immunoglobulin fragments are being currently used to produce antivenoms. However, they have low potency and are not always effective. They also possess severe adverse effects. The small size of nanobodies allows them to diffuse through the body with a biodistribution that matches that of the small venom toxin, and after the nanobody captures the venom, the complex is still small enough to be rapidly eliminated by the kidneys.

Anti-infective agents

Nanobodies can be developed as an agent against bacterial, viral, and parasitic infections. A Phase I trial of nanobodies targeting respiratory syncytial virus showed that nanobodies could fight infection. Nanobodies lack the Fc region of a conventional antibody, so they do not neutralize and eliminate the pathogen. However, they have their own inherent neutralizing effect.

Immune-based therapeutics

Nanobodies can be used to combat cancer and other diseases by inhibiting ligand-receptor interactions, such as antagonizing anti-von Willebrand factor to block the initiation of thrombosis, or inhibiting anti-TNF-α to treat arthritis.

Bispecific nanobodies

Bispecific or multispecific antibodies can target more than one antigen at a time. Because nanobodies are monomeric, single-domain molecules, and small in size, they are good candidates to construct bispecific or multispecific constructs. Bispecific antibodies have been studied for their ability to target a disease or cancer cell and also specifically recruit another molecule or cell. The same approach could be used with nanobodies because of their small size and high stability.

Further Reading

• All Nanoscience Content
• Characterization of Nanoparticles
• What are Nanomicelles?
• Applications of Nanomicelles
• Pioneering British Nanoscientists