Resources Blog The Emergence and Evolution of scFvs

The Emergence and Evolution of scFvs

Biointron 2024-05-14 Read time: 4 mins
scFv.jpg
The differences of scFv and nanobody in structure. DOI: 10.1186/s40364-021-00332-6

Antibody engineering has significantly advanced with the development of various formats that enhance therapeutic efficacy and diagnostic precision. Single-chain variable fragments (scFvs) represent one of these innovative formats. Consisting only of the variable regions of the heavy (VH) and light (VL) chains of immunoglobulins linked by a short peptide, scFvs maintain the antigen-binding ability of the parent antibody. Being 25-30 kDa in size, they are significantly smaller than a full antibody. The design of the linker is critical as it influences the stability and the binding affinity of the scFv. 

scFvs were first conceptualized and developed in the late 1980s as researchers sought to create more manageable antibody fragments for therapeutic use. These fragments were designed to overcome the limitations posed by the size and complexity of conventional monoclonal antibodies, making them suitable for applications where size and penetration into tissues are crucial. 

Timeline 

1988: A paper by Huston et al. demonstrated the design of an engineered scFv with a single polypeptide connected with a 15 amino acid linker. It showed clear specificity against digoxin, with recovery of activity in an anti-digoxin single-chain Fv analogue produced in Escherichia coli.1

1990s: Refinement of scFv technology addressed issues such as stability and solubility. There was also increasing interest in potential applications in diagnostics and therapeutics. Cheadle et al. cloned and expressed the Fv portion of a mouse myeloma protein, which was found to be biologically active with an identical affinity as that of the native Fv.2

Early 2000s: Growing use of scFvs in diagnostic applications, including immunoassays and imaging, in addition to therapeutic purposes, especially in cancer targeting. 

Mid-2000s: Introduction of bispecific scFvs, capable of binding two different antigens simultaneously. 

2010s - Present: scFvs began entering clinical trials for therapeutic applications, with ongoing research to improve stability, bioavailability, and reduce potential immunogenicity.

Altogether, scFvs have gained significant importance with applications spanning preclinical, clinical, and research domains. Progress in antibody engineering has enabled the creation of highly customized scFvs, boasting enhanced pharmacokinetic traits, thus greatly enhancing their clinical significance. 


References

  1. Huston, J. S., Levinson, D., Tai, M. S., Novotný, J., Margolies, M. N., Ridge, R. J., Bruccoleri, R. E., Haber, E., & Crea, R. (1988). Protein engineering of antibody binding sites: Recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia coli. Proceedings of the National Academy of Sciences, 85(16), 5879-5883. https://doi.org/10.1073/pnas.85.16.5879

  2. Cheadle, C., Hook, L. E., Givol, D., & Ricca, G. A. (1992). Cloning and expression of the variable regions of mouse myeloma protein MOPC315 in E. Coli: Recovery of active FV fragments. Molecular Immunology, 29(1), 21-30. https://doi.org/10.1016/0161-5890(92)90152-N

  3. María, R., Irene, E., Fernando, L., & Alfredo, A. (2022). Single-Chain Fragment Variable: Recent Progress in Cancer Diagnosis and Therapy. Cancers, 14(17), 4206. https://doi.org/10.3390/cancers14174206

Subscribe to our Blog

Recent Blog

DOI:10.1038/s41557-024-01507-y Antibody–drug conjugates (ADCs) have emerged as a revolutionary class of targeted cancer therapies, combining the specificity of monoclonal antibodies with the potent cytotoxicity of small-molecule drugs. While traditional ADCs typ

Jun 14, 2024
Blog

Antibody Engineering & Therapeutics Europe 2024 was held in London, UK on 4-6 June, 2024. As Europe's leading antibody conference for accelerating next-generation antibodies to commercial success, topics discussed included:Emerging modalities: ADCs, degraders, and beyondFc

Jun 12, 2024
Blog

The BIO International Convention 2024 was held in San Diego, CA from June 3-6. It is the largest event for biotechnology with over 18,500 industry leaders in attendance, sharing the latest advancements in the industry. The most popular topics included:AI and Digital HealthNext Generation

Jun 10, 2024
Blog

10.1038/nbt1127. DOI:10.1038/nbt1127Antibody mimetics, also known as non-immunoglobulin scaffolds, are engineered proteins designed to mimic the antigen-binding properties of antibodies. Unlike traditional antibodies, which are based on the immunoglobulin structure, antibody mimetics are derived fro

Jun 07, 2024
Blog

Our website uses cookies to improve your experience. Read our Privacy Policy to find out more.