BMB Rep. 2015; 48(9): 489-494  
Synthetic approach to the generation of antibody diversity
Hyunbo Shim*
Departments of Bioinspired Science and Life Science, Ewha Woman’s University, Seoul 03760, Korea
Correspondence to: Tel: +82-2-3277-4240; Fax: +82-2-3277-3760; E-mail:
Received: June 18, 2015; Published online: September 30, 2015.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

The in vitro antibody discovery technologies revolutionized the generation of target-specific antibodies that traditionally relied on the humoral response of immunized animals. An antibody library, a large collection of diverse, pre-constructed antibodies, can be rapidly screened using in vitro display technologies such as phage display. One of the keys to successful in vitro antibody discovery is the quality of the library diversity. Antibody diversity can be obtained either from natural B-cell sources or by the synthetic methods that combinatorially generate random nucleotide sequences. While the functionality of a natural antibody library depends largely upon the library size, various other factors can affect the quality of a synthetic antibody library, making the design and construction of synthetic antibody libraries complicated and challenging. In this review, we present various library designs and diversification methods for synthetic antibody library. From simple degenerate oligonucleotide synthesis to trinucleotide synthesis to physicochemically optimized library design, the synthetic approach is evolving beyond the simple emulation of natural antibodies, into a highly sophisticated method that is capable of producing high quality antibodies suitable for therapeutic, diagnostic, and other demanding applications.
Keywords: Antibody library, Phage display, Synthetic antibody diversity

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