Single-domain antibody

Ribbon diagram of a llama VHH domain.
The extended CDR3 loop is coloured orange.

A single-domain antibody (sdAb), also known as a Nanobody, is an antibody fragment consisting of a single monomeric variable antibody domain. Like a whole antibody, it is able to bind selectively to a specific antigen. With a molecular weight of only 12–15 kDa, single-domain antibodies are much smaller than common antibodies (150–160 kDa) which are composed of two heavy protein chains and two light chains, and even smaller than Fab fragments (~50 kDa, one light chain and half a heavy chain) and single-chain variable fragments (~25 kDa, two variable domains, one from a light and one from a heavy chain).[1]

The first single-domain antibodies were engineered from heavy-chain antibodies found in camelids; these are called VHH fragments. Cartilaginous fishes also have heavy-chain antibodies (IgNAR, 'immunoglobulin new antigen receptor'), from which single-domain antibodies called VNAR fragments can be obtained.[2] An alternative approach is to split the dimeric variable domains from common immunoglobulin G (IgG) from humans or mice into monomers. Although most research into single-domain antibodies is currently based on heavy chain variable domains, Nanobodies derived from light chains have also been shown to bind specifically to target epitopes.[3]

Camelid Nanobodies have been shown to be just as specific as antibodies, and in some cases they are more robust. They are easily isolated using the same phage panning procedure used for antibodies, allowing them to be cultured in vitro in large concentrations. The smaller size and single domain make these antibodies easier to transform into bacterial cells for bulk production, making them ideal for research purposes.[4]

Single-domain antibodies are being researched for multiple pharmaceutical applications, and have potential for use in the treatment of acute coronary syndrome, cancer, Alzheimer's disease,[5][6] and Covid-19.[7][8][9]

  1. ^ Harmsen MM, De Haard HJ (November 2007). "Properties, production, and applications of camelid single-domain antibody fragments". Applied Microbiology and Biotechnology. 77 (1): 13–22. doi:10.1007/s00253-007-1142-2. PMC 2039825. PMID 17704915.
  2. ^ English H, Hong J, Ho M (January 2020). "Ancient species offers contemporary therapeutics: an update on shark VNAR single domain antibody sequences, phage libraries and potential clinical applications". Antibody Therapeutics. 3 (1): 1–9. doi:10.1093/abt/tbaa001. PMC 7034638. PMID 32118195.
  3. ^ Möller A, Pion E, Narayan V, Ball KL (December 2010). "Intracellular activation of interferon regulatory factor-1 by nanobodies to the multifunctional (Mf1) domain". The Journal of Biological Chemistry. 285 (49): 38348–38361. doi:10.1074/jbc.M110.149476. PMC 2992268. PMID 20817723.
  4. ^ Ghannam A, Kumari S, Muyldermans S, Abbady AQ (March 2015). "Camelid nanobodies with high affinity for broad bean mottle virus: a possible promising tool to immunomodulate plant resistance against viruses". Plant Molecular Biology. 87 (4–5): 355–369. doi:10.1007/s11103-015-0282-5. PMID 25648551. S2CID 17578111.
  5. ^ "Nanobodies herald a new era in cancer therapy". The Medical News. 12 May 2004.
  6. ^ "Pipeline". Ablynx. Retrieved 20 January 2010.
  7. ^ Gill, Victoria (22 September 2021). "Covid: Immune therapy from llamas shows promise". BBC News.
  8. ^ Buffington J, Duan Z, Kwon HJ, Hong J, Li D, Feng M, et al. (June 2023). "Identification of nurse shark VNAR single-domain antibodies targeting the spike S2 subunit of SARS-CoV-2". FASEB Journal. 37 (6): e22973. doi:10.1096/fj.202202099RR. PMC 10715488. PMID 37191949. S2CID 258717083.
  9. ^ Hong J, Kwon HJ, Cachau R, Chen CZ, Butay KJ, Duan Z, et al. (May 2022). "Dromedary camel nanobodies broadly neutralize SARS-CoV-2 variants". Proceedings of the National Academy of Sciences of the United States of America. 119 (18): e2201433119. Bibcode:2022PNAS..11901433H. doi:10.1073/pnas.2201433119. PMC 9170159. PMID 35476528.