Advantages and limitation of Nanobodies (single domain antibodies)


Nanobodies are frequently compared to polyclonal, monoclonal antibodies, antibody fragments, and small molecules. The production of nanobodies is simple and cost effective compared to the polyclonal antibodies. Besides, Nbs are stable in a wide range of temperatures and pH levels. Nanobodies are also compatible with genetic engineering methods, which allow scaffolding and alteration of amino acids to improve binding. Relating to structure, the hydrophilic side of nanobodies, that is not present in conventional antibodies, means they do not have issues with solubility and aggregation. The conventional antibodies do not bind well in grooves or cavities on the surface of the antigen. But, Nanobodies bind with the clefts of the active site of antigen. Since, nanobodies still have some limitations and disadvantages. The nanobodies can be developed only from camelids and sharks. Traditional monoclonal antibodies, on the other hand, are obtained from mice. Therefore, the development of nanobodies requires larger, more complicated housing and animal husbandry for obtaining the desired antibody. The advantages and limitations of nanobodies and antibodies are shown in table 1.

Size150 kD15 kD
Development costsHighModerate
Administrationi.v., s.c.i.v., s.c., aerosol, topical
Off target adverse effectsNoneNone
In Vivo half-lifeCan be adjusted by Fc-engineeringCan be adjusted by PEGylation or fusion to albumin-specific Nb
MetabolitesNon-toxic, biodegradableNon-toxic, biodegradable
Tissue penetrationSlowExcellent in periphery
Tissue specificityTargetable (bi-specific Abs)Targetable (bi- specific Nbs)
Albumin bindingUsually notVia albumin-specific Nb to extend half-life, usually no effect on potency