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| <L-07>:Life Science, Pharmaceutical Sciences |
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Rapid Development Technology for Humanized Single-Domain Antibodies
― A New Modality for Biosensor and Therapeutic Antibody Development ―
| Akikazu Murakami |
Associate Professor |
| Department of Oral Microbiology, Basic Dentistry, Oral Science, Graduate School of Biomedical Sciences |
| Keywords |
Therapeutic antibodies, single-domain antibodies, phage display |
| Laboratory URL |
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| Research Overview |
● Single-Domain Antibodies (sdAbs): Superior Physicochemical Properties and Cost-Effective Mass Production, but Animal Immunization as a Bottleneck
In recent years, antibodies composed solely of heavy chains have been discovered in camelids and cartilaginous fishes. It has been shown that a single domain with a molecular weight of approximately 15 kDa can specifically bind to target antigens. Antibodies developed based on this concept, known as single-domain antibodies (sdAbs), are small in size, highly stable against heat and denaturants, and can be produced inexpensively and in large quantities using organisms such as Escherichia coli. Furthermore, they offer numerous advantages, including ease of modification and fusion with other molecules. However, their development requires the immunization and maintenance of large animals, which entails significant cost, effort, and time.
● Technical Challenge: Construction of a Highly Diverse Antibody Gene Library to Bypass Animal Breeding and Immunization
Using an original approach, we constructed a phage-displayed sdAb library with a diversity exceeding 4 × 1010, based on genes derived from alpaca B cells. This system enables the rapid acquisition of sdAbs against a wide variety of antigens without the need for animal immunization.
Furthermore, to facilitate the application of sdAbs as therapeutic antibodies, we are currently developing a rapid and user-friendly humanization technology.
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| Potential Applications and Commercialization Prospects |
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● Biosensors and Therapeutic Antibody Development Enabled by Humanization TechnologyAntibodies obtained from the library can be utilized in a broad range of applications, including research reagents for ELISA and Western blotting, diagnostic reagents such as immunochromatographic assays, and biosensors integrated into analytical devices.
In addition, through humanization technology, these antibodies can be applied as therapeutic agents. Beyond conventional antibody drugs, potential applications include multispecific antibodies, intracellularly functional antibodies, and components of chimeric antigen receptors (CARs).
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| Publications |
● Akikazu Murakami et al., An alpaca single domain antibody (VHH) phage display library constructed by CDR shuffling provided high affinity VHHs against desired protein antigens, International immunology, Volume 34, Issue 8, (2022)
● Akikazu Murakami, Yusuke Nakajima.
Industrial applications of single-domain antibodies using synthetic library and molecular evolution methods. Enzyme Engineering News, No. 87, pp. 21–25, April 2022. |
Last updated date:October 15, 2026