Why nanobodies?

Conventional antibodies are remarkably successful molecules for biomedical applications and have been of common use for medical applications. They are structurally complex, large hetero-tetrameric proteins consisting of two heavy chains and two light chains. The heavy chain comprises three constant domains (CH1 – CH3) and one variable domain (VH), whereas the light chain comprises one constant domain (CL) and one variable domain (VL). Antigen binding is mediated by the variable domains of each chain.

However, for distinct applications, their efficacy might be impaired by reason of their inherent attributes. For instance, they are large molecules (~150 kDa), which limits their tissue and/or tumor penetration and biodistribution. Second, they can elicit immune reactions that neutralize their activities, which sometimes limits the long-term use of chimeric and humanized antibodies available on the market. Third, they typically have a serum half-life of several days and this limits their use in molecular imaging because of the intense background signal. Additionally, they are difficult and expensive to produce, which imposes a heavy burden on healthcare and research budgets.

Nanobody, also called single-domain antibody, is the variable region isolated from the antigen-binding variable domain (VHH) of camelid heavy-chain-only antibody or the variable domain (vNAR) of cartilaginous fish immunoglobulin new antigen receptor (IgNAR). With a size of just 12~15 kDa (2~4 nm), nanobody is the smallest antigen-binding fragment discovered today and holds a plethora of intrinsic advantages over conventional monoclonal antibodies.

Nanobody owns a simple architecture, high thermal and chemical stability, good solubility, high tissue penetration, and easy modularity, and offers large-scale production possibilities. Nanobodies are becoming a key component in a variety of areas of research, such as medical diagnosis, therapy, precision medicine, and basic research. 

Discover the groundbreaking realm of nanobodies by delving into the comprehensive article “Single Domain Antibody: Advantages and Applications in Pharma” on Pharma Focus Asia’s website (https://www.pharmafocusasia.com/articles/single-domain-antibody).

Characteristics Nanobody Conventional antibody
Size ~ 12~15 kDa ~ 150 kDa
Binding affinity pM to nM ranged kD nM to µM ranged kD
Batch to batch consistency Very high High (subjected to genetic drift)
Novel epitope Yes N/A
Solubility (aggregation escape) High Very poor
Stability (temperature and pH) High Low