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10.1080/19420862.2018.1426422 http://scihub22266oqcxt.onion/10.1080/19420862.2018.1426422 C5916548!5916548 !29376776     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29376776 &cmd=llinks): Failed to open stream: HTTP request failed! 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A natively paired antibody library yields drug leads with higher sensitivity and specificity than a randomly paired antibody library |pdf=|usr=}}{{29376776 }} gab.com Text A natively paired antibody library yields drug leads with higher sensitivity and specificity than a randomly paired antibody library JO: MAbs http://www.kidney.de/pget.php?&tw=1&pmid=29376776 #FOAvip Deep sequencing and single-chain variable fragment (scFv) yeast display methods are becoming more popular for discovery of therapeutic antibody candidates in mouse B cell repertoires. In this study, we compare a deep sequencing and scFv display method that retains native heavy and light chain pairing with a related method that randomly pairs heavy and light chain. We performed the studies in a humanized mouse, using interleukin 21 receptor (IL-21R) as a test immunogen. We identified 44 high-affinity binder scFv with the native pairing method and 100 high-affinity binder scFv with the random pairing method. 30% of the natively paired scFv binders were also discovered with the randomly paired method, and 13% of the randomly paired binders were also discovered with the natively paired method. Additionally, 33% of the scFv binders discovered only in the randomly paired library were initially present in the natively paired pre-sort library. Thus, a significant proportion of "randomly paired" scFv were actually natively paired. We synthesized and produced 46 of the candidates as full-length antibodies and subjected them to a panel of binding assays to characterize their therapeutic potential. 87% of the antibodies were verified as binding IL-21R by at least one assay. We found that antibodies with native light chains were more likely to bind IL-21R than antibodies with non-native light chains, suggesting a higher false positive rate for antibodies from the randomly paired library. Additionally, the randomly paired method failed to identify nearly half of the true natively paired binders, suggesting a higher false negative rate. We conclude that natively paired libraries have critical advantages in sensitivity and specificity for antibody discovery programs. Twit Text FOAVip A natively paired antibody library yields drug leads with higher sensitivity and specificity than a randomly paired antibody library ????MAbs http://www.kidney.de/pget.php?&tw=1&pmid=29376776 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29376776 #FOAvip English Wikipedia <ref>{{Cite pmid|29376776 }}</ref> A natively paired antibody library yields drug leads with higher sensitivity and specificity than a randomly paired antibody library #MMPMID29376776 Adler AS ; Bedinger D ; Adams MS ; Asensio MA ; Edgar RC ; Leong R ; Leong J ; Mizrahi RA ; Spindler MJ ; Bandi SR ; Huang H ; Tawde P ; Brams P ; Johnson DS MAbs 2018[Apr]; 10 (3 ): 431-443 PMID29376776 show ga Deep sequencing and single-chain variable fragment (scFv) yeast display methods are becoming more popular for discovery of therapeutic antibody candidates in mouse B cell repertoires. In this study, we compare a deep sequencing and scFv display method that retains native heavy and light chain pairing with a related method that randomly pairs heavy and light chain. We performed the studies in a humanized mouse, using interleukin 21 receptor (IL-21R) as a test immunogen. We identified 44 high-affinity binder scFv with the native pairing method and 100 high-affinity binder scFv with the random pairing method. 30% of the natively paired scFv binders were also discovered with the randomly paired method, and 13% of the randomly paired binders were also discovered with the natively paired method. Additionally, 33% of the scFv binders discovered only in the randomly paired library were initially present in the natively paired pre-sort library. Thus, a significant proportion of "randomly paired" scFv were actually natively paired. We synthesized and produced 46 of the candidates as full-length antibodies and subjected them to a panel of binding assays to characterize their therapeutic potential. 87% of the antibodies were verified as binding IL-21R by at least one assay. We found that antibodies with native light chains were more likely to bind IL-21R than antibodies with non-native light chains, suggesting a higher false positive rate for antibodies from the randomly paired library. Additionally, the randomly paired method failed to identify nearly half of the true natively paired binders, suggesting a higher false negative rate. We conclude that natively paired libraries have critical advantages in sensitivity and specificity for antibody discovery programs. |*Gene Library [MESH] |*Immunoglobulin Light Chains/biosynthesis/genetics/immunology [MESH] |*Interleukin-21 Receptor alpha Subunit/antagonists & inhibitors/immunology [MESH] |*Single-Chain Antibodies/genetics/immunology [MESH] |Animals [MESH] |B-Lymphocytes/*immunology [MESH] |Humans [MESH]A natively paired antibody library yields drug leads with higher sensi(epmc).pdf DeepDyve Pubget Overpricing