A Novel Human scFv Library with Non-Combinatorial Synthetic CDR Diversity.
The present work describes the construction and validation of a human scFv library with a novel design approach to synthetic complementarity determining region (CDR) diversification. The advantage of synthetic antibody libraries includes the possibility of exerting fine control over factors like fra...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4613135?pdf=render |
| _version_ | 1828827508270694400 |
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| author | Xuelian Bai Jihye Kim Seungmin Kang Wankyu Kim Hyunbo Shim |
| author_facet | Xuelian Bai Jihye Kim Seungmin Kang Wankyu Kim Hyunbo Shim |
| author_sort | Xuelian Bai |
| collection | DOAJ |
| description | The present work describes the construction and validation of a human scFv library with a novel design approach to synthetic complementarity determining region (CDR) diversification. The advantage of synthetic antibody libraries includes the possibility of exerting fine control over factors like framework sequences, amino acid and codon usage, and CDR diversity. However, random combinatorial synthesis of oligonucleotides for CDR sequence diversity also produces many clones with unnatural sequences and/or undesirable modification motifs. To alleviate these issues, we designed and constructed a novel semi-synthetic human scFv library with non-combinatorial, pre-designed CDR diversity and a single native human framework each for heavy, kappa, and lambda chain variable domains. Next-generation sequencing analysis indicated that the library consists of antibody clones with highly nature-like CDR sequences and the occurrence of the post-translational modification motifs is minimized. Multiple unique clones with nanomolar affinity could be isolated from the library against a number of target antigens, validating the library design strategy. The results demonstrate that it is possible to construct a functional antibody library using low, non-combinatorial synthetic CDR diversity, and provides a new strategy for the design of antibody libraries suitable for demanding applications. |
| first_indexed | 2024-12-12T15:00:42Z |
| format | Article |
| id | doaj.art-3de71922a2d947db96f5ab00b1b1c5a2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T15:00:42Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3de71922a2d947db96f5ab00b1b1c5a22022-12-22T00:20:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e014104510.1371/journal.pone.0141045A Novel Human scFv Library with Non-Combinatorial Synthetic CDR Diversity.Xuelian BaiJihye KimSeungmin KangWankyu KimHyunbo ShimThe present work describes the construction and validation of a human scFv library with a novel design approach to synthetic complementarity determining region (CDR) diversification. The advantage of synthetic antibody libraries includes the possibility of exerting fine control over factors like framework sequences, amino acid and codon usage, and CDR diversity. However, random combinatorial synthesis of oligonucleotides for CDR sequence diversity also produces many clones with unnatural sequences and/or undesirable modification motifs. To alleviate these issues, we designed and constructed a novel semi-synthetic human scFv library with non-combinatorial, pre-designed CDR diversity and a single native human framework each for heavy, kappa, and lambda chain variable domains. Next-generation sequencing analysis indicated that the library consists of antibody clones with highly nature-like CDR sequences and the occurrence of the post-translational modification motifs is minimized. Multiple unique clones with nanomolar affinity could be isolated from the library against a number of target antigens, validating the library design strategy. The results demonstrate that it is possible to construct a functional antibody library using low, non-combinatorial synthetic CDR diversity, and provides a new strategy for the design of antibody libraries suitable for demanding applications.http://europepmc.org/articles/PMC4613135?pdf=render |
| spellingShingle | Xuelian Bai Jihye Kim Seungmin Kang Wankyu Kim Hyunbo Shim A Novel Human scFv Library with Non-Combinatorial Synthetic CDR Diversity. PLoS ONE |
| title | A Novel Human scFv Library with Non-Combinatorial Synthetic CDR Diversity. |
| title_full | A Novel Human scFv Library with Non-Combinatorial Synthetic CDR Diversity. |
| title_fullStr | A Novel Human scFv Library with Non-Combinatorial Synthetic CDR Diversity. |
| title_full_unstemmed | A Novel Human scFv Library with Non-Combinatorial Synthetic CDR Diversity. |
| title_short | A Novel Human scFv Library with Non-Combinatorial Synthetic CDR Diversity. |
| title_sort | novel human scfv library with non combinatorial synthetic cdr diversity |
| url | http://europepmc.org/articles/PMC4613135?pdf=render |
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