KMD Bioscience Co., Ltd.
400-621-6806
2020-12-17 Hits(888)
Nanobodies are single-domain antibodies that contain the unique structural and functional properties of naturally-occurring heavy chain in camelidae. As a novel class of antibody, they show many advantages compared with traditional antibodies such as smaller size, higher stability, improved specificity, more easily expressed in microorganisms. These unusual hallmarks make them as promising tools in basic research and clinical practice.
1. Introduction to Nanobodies
The antibodies in our blood, and in most other vertebrate animals, are composed of two types of chains. The larger heavy chain plays two roles. It comes together with another heavy chain, forming the stem of the Y-shaped antibody. It also associates with two smaller light chains, which together create the antigen-binding site at the tips of each arm. Some of the antibodies in camels, however, do without the light chains entirely. The two arms are composed of a truncated version of the heavy chain, and the single domain in each arm does all the work of recognizing antigens.
Nanobodies are similar fragments taken from the unusual camel antibodies. The Nanobody technology was originally developed following the discovery and identification that camelidae (e.g. camels and llamas) possess fully functional antibodies that consist of heavy chains only and therefore lack light chains. These heavy-chain only antibodies contain a single variable domain(VHH) and two constant domains (CH2, CH3). The arms are cut off, creating a smaller, more stable molecule that, like an antibody Fab, is highly specific for a given target molecule.
The cloned and isolated single variable domains have full antigen binding capacity and are very stable. These single variable domains, with their unique structural and functional properties, form the basis of a new generation of therapeutic molecules which Ablynx has named “Nanobodies”.
Fig. 1. The structure of Nanobody
2. Characteristics for Nanobodies
Nanobodies have high heat resistance and stability. Comparing the antigen binding activity of mouse monoclonal antibody and Nanobody at high temperature of 90 ℃ for a long time, it was found that Nanobody maintained high activity and could still regain antigen binding ability, while all conventional antibodies lost after 90 ℃ treatment In order to become active, an irreversible polymerization occurred.
Nanobodies have strong tissue penetration because of small molecular weight. Nanobodies have strong and fast tissue penetration ability, and can enter dense tissues such as solid tumors to play a role; and excess unbound nanobodies can be quickly removed, that is more conducive to the diagnosis of the disease. Compared to monoclonal antibodies, which have poor tissue penetration, can not be easy to clear the deficiencies. In addition, Nanobodies can effectively penetrate the blood-brain barrier, this feature provides a new method for brain drug delivery, and is expected to become a new drug for the treatment of Alzheimer's disease.
Nanobodies also have high water solubility and high expression. Nanobodies are easy to synthesize in microbes because of their small molecular weight, simple structure, and are encoded by a single gene. They can be expressed in large amounts in bacteriophages, yeasts, and other microorganisms. They are relatively inexpensive, can be mass-produced, and are easy to popularize.
Nanobodies easily form new fusion molecules with other structures (such as BSA, IgG-Fc etc.). In the new fusion molecule, Nanobodies bind to their target antigens, and the part fused with Nanobodies can play the corresponding function, so they can be used in combination with other drugs, or used in diagnostics and as an experimental research tool in various fields , The application scenarios are vast. Conceptually, Nanobodies have already been verified. The second new drug approved by the US FDA in 2019 is a nanobody. And the latest research shows that the Nanobody in the alpaca has the potential to eliminate the COVID–19.
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