Current Biotechnology ›› 2025, Vol. 15 ›› Issue (6): 969-976.DOI: 10.19586/j.2095-2341.2025.0063
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Received:2025-05-16
Accepted:2025-09-05
Online:2025-11-25
Published:2026-01-04
Contact:
Weihong TAO
CLC Number:
Xue MIN, Weihong TAO. The Appliation Advance of Fab Synthetic Libraries with Phage Display in Antibody Discovery[J]. Current Biotechnology, 2025, 15(6): 969-976.
闵雪, 陶维红. Fab合成噬菌体文库在抗体发现领域的应用进展[J]. 生物技术进展, 2025, 15(6): 969-976.
| 抗体名称 | FDA批准年 | 公司名称 | 靶点;形式 | 展示形式 | 抗体库类型 | 参考文献 |
|---|---|---|---|---|---|---|
| Adalimumab | 2002年 | AbbVie | TNF;人源化IgG1 | 天然scFv | CAT | [ |
| Atezolizumab | 2016年 | Roche | PD-L1 型;人源化IgG1 | 合成Fab | Genentech | [ |
| Avelumab | 2017年 | Merck KGaA/Pfizer | PD-L1型;人源化IgG1 | 天然Fab | 天然Fab库 | [ |
| Belimumab | 2011年 | GSK/HGS | BLyS;人源化IgG1 | 天然scFv | CAT | [ |
| Emapalumab | 2018年 | NovImmuneSA | IFNγ;人源化IgG1 | 天然scFv | CAT | [ |
| Guselkumab | 2017年 | Janssen | IL-23 P19;人源化IgG1 | 合成Fab | Morphosys' HuCAL GOLD | [ |
| Ixekizumab | 2016年 | Eli Lilly | IL-17a;人源化IgG4 | 免疫Fab | EliLilly | [ |
| Lanadelumab | 2018年 | HGS | 血浆激肽释放酶;人源化IgG1 | 天然Fab | Dyax | [ |
| Mirikizumab | 2023年 | Eli Lilly | IL-23p19;人源化IgG4 | 合成Fab | 合成Fab文库 | [ |
| Moxetumomabpasudotox | 2018年 | MedImmune | CD22;鼠源IgG1 dsFv免疫毒素 | 天然scFv | CAT | [ |
| Necitumumab | 2015年 | Eli Lilly | EGFR脂肪酸;人源化IgG1 | 天然Fab | Dyax | [ |
| Polatuzumab vedotin | 2019年 | Roche | CD79b;人源化IgG1 ADC | 合成Fab | 半合成Fab库 | [ |
| Ramucirumab | 2014年 | EliLilly | VEGFR2;人源化IgG1 | 天然Fab | Dyax | [ |
| Ranibizumab | 2006年 | Roche/Novartis | VEGF;人源化IgG1 Fab | 合成Fab | Genentech | [ |
| Raxibacumab | 2012年 | GSK/HGS | 炭疽芽孢杆菌保护性抗原;人源化IgG1 | 天然scFv | CAT | [ |
| Risankizumab | 2019年 | Abbvie | IL-23p19;人源化IgG1 | 合成Fab | 半合成Fab库 | [ |
| Spesolimab | 2022年 | Boehringer Ingelheim | IL-36受体;人源化IgG1 | 合成Fab | 合成Fab库 | [ |
| Tebentafusp | 2022年 | Immunocore | gp100, CD3;TCR-scFv | 合成scFv | 半合成scFv库 | [ |
| Tralokinumab | 2021年 | AstraZeneca | IL-13;人源化IgG4 | 天然scFv | CAT | [ |
| Zenocutuzumab | 2024年 | Merus | HER2、HER3;人源化IgG1 | 合成Fab | 半合成Fab库 | [ |
Table 1 Approved phage-derived antibodies
| 抗体名称 | FDA批准年 | 公司名称 | 靶点;形式 | 展示形式 | 抗体库类型 | 参考文献 |
|---|---|---|---|---|---|---|
| Adalimumab | 2002年 | AbbVie | TNF;人源化IgG1 | 天然scFv | CAT | [ |
| Atezolizumab | 2016年 | Roche | PD-L1 型;人源化IgG1 | 合成Fab | Genentech | [ |
| Avelumab | 2017年 | Merck KGaA/Pfizer | PD-L1型;人源化IgG1 | 天然Fab | 天然Fab库 | [ |
| Belimumab | 2011年 | GSK/HGS | BLyS;人源化IgG1 | 天然scFv | CAT | [ |
| Emapalumab | 2018年 | NovImmuneSA | IFNγ;人源化IgG1 | 天然scFv | CAT | [ |
| Guselkumab | 2017年 | Janssen | IL-23 P19;人源化IgG1 | 合成Fab | Morphosys' HuCAL GOLD | [ |
| Ixekizumab | 2016年 | Eli Lilly | IL-17a;人源化IgG4 | 免疫Fab | EliLilly | [ |
| Lanadelumab | 2018年 | HGS | 血浆激肽释放酶;人源化IgG1 | 天然Fab | Dyax | [ |
| Mirikizumab | 2023年 | Eli Lilly | IL-23p19;人源化IgG4 | 合成Fab | 合成Fab文库 | [ |
| Moxetumomabpasudotox | 2018年 | MedImmune | CD22;鼠源IgG1 dsFv免疫毒素 | 天然scFv | CAT | [ |
| Necitumumab | 2015年 | Eli Lilly | EGFR脂肪酸;人源化IgG1 | 天然Fab | Dyax | [ |
| Polatuzumab vedotin | 2019年 | Roche | CD79b;人源化IgG1 ADC | 合成Fab | 半合成Fab库 | [ |
| Ramucirumab | 2014年 | EliLilly | VEGFR2;人源化IgG1 | 天然Fab | Dyax | [ |
| Ranibizumab | 2006年 | Roche/Novartis | VEGF;人源化IgG1 Fab | 合成Fab | Genentech | [ |
| Raxibacumab | 2012年 | GSK/HGS | 炭疽芽孢杆菌保护性抗原;人源化IgG1 | 天然scFv | CAT | [ |
| Risankizumab | 2019年 | Abbvie | IL-23p19;人源化IgG1 | 合成Fab | 半合成Fab库 | [ |
| Spesolimab | 2022年 | Boehringer Ingelheim | IL-36受体;人源化IgG1 | 合成Fab | 合成Fab库 | [ |
| Tebentafusp | 2022年 | Immunocore | gp100, CD3;TCR-scFv | 合成scFv | 半合成scFv库 | [ |
| Tralokinumab | 2021年 | AstraZeneca | IL-13;人源化IgG4 | 天然scFv | CAT | [ |
| Zenocutuzumab | 2024年 | Merus | HER2、HER3;人源化IgG1 | 合成Fab | 半合成Fab库 | [ |
| 抗体库名称 | 抗体形式 | 文库容量 | 最佳亲和力KD/(nmol·L-1) | V基因来源 | 框架 | 技术 | 参考文献 |
|---|---|---|---|---|---|---|---|
| CAT1.0 | 天然scFv | 1.4×1010 | 0.3 | 健康供体的PBLs、扁桃体、骨髓B细胞 | — | 随机引物扩增;两片段PCR建库 | [ |
| CAT2.0 | 天然scFv | 1.29×1011 | 0.09 | CAT1.0文库基因、健康供体脾脏、胎儿肝组织B细胞 | — | 种系特异性引物扩增 | [ |
| n | 天然scFv | 2×109 | 0.9 | 健康供体的PBMC、脾脏、扁桃体、淋巴结B细胞 | — | 重叠延伸PCR技术 | [ |
| Dyax | 半合成Fab | 3.5×1010 | 0.22 | 自身免疫病患者的PBMC | VH3-23基因片段框架 | ONCL技术;密码子突变技术 | [ |
| Morphosys'HuCAL | 全合成scFv | 2×107 | 0.082 | 49对VH/VLHuCAL共识框架 | TRIM技术 | [ | |
| Morphosys'HuCAL GOLD | 全合成Fab | 1.6×1010 | 0.04 | 49对VH/VL优化的HuCAL共识框架 | TRIM技术;CysDisplay技术 | [ | |
| Morphosys'HuCAL PLATINUM | 全合成Fab | 4.5×1010 | 0.002 | 42对VH/VL框架基因序列 | TRIM技术 | [ | |
| MorphoSys’Ylanthia | 全合成Fab | 1.3×1011 | 0.7 | Ig V基因序列数据库 | 36对VH/VL固定框架 | TRIM技术;Slonomics技术 | [ |
| PHILODiamond | 全合成scFv | 4.1×1010 | 27 | 蛋白A亲和层析筛选技术 | [ | ||
| ALTHEA Gold | 半合成scFv | 2.5×1010 | 0.094 | 健康供体的PBMC | IGHV和IGKV胚系基因框架 | 三聚体亚磷酰胺技术;蛋白A亲和层析筛选技术;NGS技术 | [ |
Table 2 Features of commonly used large antibody libraries
| 抗体库名称 | 抗体形式 | 文库容量 | 最佳亲和力KD/(nmol·L-1) | V基因来源 | 框架 | 技术 | 参考文献 |
|---|---|---|---|---|---|---|---|
| CAT1.0 | 天然scFv | 1.4×1010 | 0.3 | 健康供体的PBLs、扁桃体、骨髓B细胞 | — | 随机引物扩增;两片段PCR建库 | [ |
| CAT2.0 | 天然scFv | 1.29×1011 | 0.09 | CAT1.0文库基因、健康供体脾脏、胎儿肝组织B细胞 | — | 种系特异性引物扩增 | [ |
| n | 天然scFv | 2×109 | 0.9 | 健康供体的PBMC、脾脏、扁桃体、淋巴结B细胞 | — | 重叠延伸PCR技术 | [ |
| Dyax | 半合成Fab | 3.5×1010 | 0.22 | 自身免疫病患者的PBMC | VH3-23基因片段框架 | ONCL技术;密码子突变技术 | [ |
| Morphosys'HuCAL | 全合成scFv | 2×107 | 0.082 | 49对VH/VLHuCAL共识框架 | TRIM技术 | [ | |
| Morphosys'HuCAL GOLD | 全合成Fab | 1.6×1010 | 0.04 | 49对VH/VL优化的HuCAL共识框架 | TRIM技术;CysDisplay技术 | [ | |
| Morphosys'HuCAL PLATINUM | 全合成Fab | 4.5×1010 | 0.002 | 42对VH/VL框架基因序列 | TRIM技术 | [ | |
| MorphoSys’Ylanthia | 全合成Fab | 1.3×1011 | 0.7 | Ig V基因序列数据库 | 36对VH/VL固定框架 | TRIM技术;Slonomics技术 | [ |
| PHILODiamond | 全合成scFv | 4.1×1010 | 27 | 蛋白A亲和层析筛选技术 | [ | ||
| ALTHEA Gold | 半合成scFv | 2.5×1010 | 0.094 | 健康供体的PBMC | IGHV和IGKV胚系基因框架 | 三聚体亚磷酰胺技术;蛋白A亲和层析筛选技术;NGS技术 | [ |
| [1] | 杨懿祺,张志高,游小龙,等.抗体药物的发展与应用[J].生物技术进展,2022,12(3):358-365. |
| YANG Y Q, ZHANG Z G, YOU X L, et al.. Development and application of monoclonal antibody-based drug[J]. Curr. Biotechnol., 2022, 12(3): 358-365. | |
| [2] | 刘碧霞, 刘媛, 谢静, 等. 噬菌体展示技术在全人源性抗体发现中的应用[J]. 免疫学杂志, 2023, 39(10):910-915. |
| LIU B X, LIU Y, XIE J, et al.. Progresses of phage display technology application in fully human antibody discovery[J]. J. Immunol., 2023, 39(10): 910-915. | |
| [3] | SMITH G P. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface[J]. Science, 1985, 228(4705): 1315-1317. |
| [4] | DEVLIN J J, PANGANIBAN L C, DEVLIN P E. Random peptide libraries: a source of specific protein binding molecules[J]. Science, 1990, 249(4967): 404-406. |
| [5] | HUSE W D, SASTRY L, IVERSON S A, et al.. Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda[J]. Science, 1989, 246(4935): 1275-1281. |
| [6] | MCCAFFERTY J, GRIFFITHS A D, WINTER G, et al.. Phage antibodies: filamentous phage displaying antibody variable domains[J]. Nature, 1990, 348(6301): 552-554. |
| [7] | BARBAS C F, KANG A S, LERNER R A, et al.. Assembly of combinatorial antibody libraries on phage surfaces: the gene Ⅲ site[J]. Proc. Natl. Acad. Sci. USA, 1991, 88(18): 7978-7982. |
| [8] | BREITLING F, DÜBEL S, SEEHAUS T, et al.. A surface expression vector for antibody screening[J]. Gene, 1991, 104(2): 147-153. |
| [9] | FRENZEL A, SCHIRRMANN T, HUST M. Phage display-derived human antibodies in clinical development and therapy[J]. mAbs, 2016, 8(7): 1177-1194. |
| [10] | HERBST R S, CSORIA J, KOWANETZ M, et al.. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients[J]. Nature, 2014, 515(7528): 563-567. |
| [11] | SHIM H. Therapeutic antibodies by phage display[J]. Curr. Pharm. Des., 2016, 22(43): 6538-6559. |
| [12] | STOHL W, HILBERT D M. The discovery and development of belimumab: the anti-BLyS-lupus connection[J]. Nat. Biotechnol., 2012, 30(1): 69-77. |
| [13] | AL-SALAMA Z T. Emapalumab: first global approval[J]. Drugs, 2019, 79(1): 99-103. |
| [14] | MARKHAM A. Guselkumab: first global approval[J]. Drugs, 2017, 77(13): 1487-1492. |
| [15] | LIU L, LU J, ALLAN B W, et al.. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A[J]. J. Inflamm. Res., 2016, 9: 39-50. |
| [16] | KENNISTON J A, FAUCETTE R R, MARTIK D, et al.. Inhibition of plasma kallikrein by a highly specific active site blocking antibody[J]. J. Biol. Chem., 2014, 289(34): 23596-23608. |
| [17] | STEERE B, BEIDLER C, MARTIN A, et al.. Generation and characterization of mirikizumab, a humanized monoclonal antibody targeting the p19 subunit of IL-23[J]. J. Pharmacol. Exp. Ther., 2023, 387(2): 180-187. |
| [18] | KREITMAN R J, PASTAN I. Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox[J]. Clin. Cancer Res., 2011, 17(20): 6398-6405. |
| [19] | LI S, KUSSIE P, FERGUSON K M. Structural basis for EGF receptor inhibition by the therapeutic antibody IMC-11F8[J]. Structure, 2008, 16(2): 216-227. |
| [20] | DORNAN D, BENNETT F, CHEN Y, et al.. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma[J]. Blood, 2009, 114(13): 2721-2729. |
| [21] | LU D, JIMENEZ X, ZHANG H, et al.. Selection of high affinity human neutralizing antibodies to VEGFR2 from a large antibody phage display library for antiangiogenesis therapy[J]. Int. J. Cancer, 2002, 97(3): 393-399. |
| [22] | CHEN Y, WIESMANN C, FUH G, et al.. Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen[J]. J. Mol. Biol., 1999, 293(4): 865-881. |
| [23] | MAZUMDAR S. Raxibacumab[J]. mAbs, 2009, 1(6): 531-538. |
| [24] | SINGH S, KROE-BARRETT R R, CANADA K A, et al.. Selective targeting of the IL23 pathway: generation and characterization of a novel high-affinity humanized anti-IL23A antibody[J]. mAbs, 2015, 7(4): 778-791. |
| [25] | MORITA A, OKUBO Y, IMAFUKU S, et al.. Spesolimab, the first-in-class anti-IL-36R antibody: from bench to clinic[J]. J. Dermatol., 2024, 51(11): 1379-1391. |
| [26] | LIDDY N, BOSSI G, ADAMS K J, et al.. Monoclonal TCR-redirected tumor cell killing[J]. Nat. Med., 2012, 18(6): 980-987. |
| [27] | MAY R D, MONK P D, COHEN E S, et al.. Preclinical development of CAT-354, an IL-13 neutralizing antibody, for the treatment of severe uncontrolled asthma[J]. Br. J. Pharmacol., 2012, 166(1): 177-193. |
| [28] | GEUIJEN C A W, DE NARDIS C, MAUSSANG D, et al.. Unbiased combinatorial screening identifies a bispecific IgG1 that potently inhibits HER3 signaling via HER2-guided ligand blockade[J]. Cancer Cell, 2021, 39(8): 1163-1164. |
| [29] | LLORENTE M, SÁNCHEZ-PALOMINO S, MAÑES S, et al.. Natural human antibodies retrieved by phage display libraries from healthy donors: polyreactivity and recognition of human immunodeficiency virus type 1gp120 epitopes[J]. Scand. J. Immunol., 1999, 50(3): 270-279. |
| [30] | LAI J Y, LIM T S. Infectious disease antibodies for biomedical applications: a mini review of immune antibody phage library repertoire[J]. Int. J. Biol. Macromol., 2020, 163: 640-648. |
| [31] | VAUGHAN T J, WILLIAMS A J, PRITCHARD K, et al.. Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library[J]. Nat. Biotechnol., 1996, 14(3): 309-314. |
| [32] | LLOYD C, LOWE D, EDWARDS B, et al.. Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens[J]. Protein Eng. Des. Sel., 2009, 22(3): 159-168. |
| [33] | SÖDERLIND E, STRANDBERG L, JIRHOLT P, et al.. Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries[J]. Nat. Biotechnol., 2000, 18(8): 852-856. |
| [34] | HOET R M, COHEN E H, KENT R B, et al.. Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity-determining-region diversity[J]. Nat. Biotechnol., 2005, 23(3): 344-348. |
| [35] | KNAPPIK A, GE L, HONEGGER A, et al.. Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides[J]. J. Mol. Biol., 2000, 296(1): 57-86. |
| [36] | ROTHE C, URLINGER S, LÖHNING C, et al.. The human combinatorial antibody library HuCAL GOLD combines diversification of all six CDRs according to the natural immune system with a novel display method for efficient selection of high-affinity antibodies[J]. J. Mol. Biol., 2008, 376(4): 1182-1200. |
| [37] | PRASSLER J, THIEL S, PRACHT C, et al.. HuCAL PLATINUM, a synthetic Fab library optimized for sequence diversity and superior performance in mammalian expression systems[J]. J. Mol. Biol., 2011, 413(1): 261-278. |
| [38] | TILLER T, SCHUSTER I, DEPPE D, et al.. A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties[J]. mAbs, 2013, 5(3): 445-470. |
| [39] | WEBER M, BUJAK E, PUTELLI A, et al.. A highly functional synthetic phage display library containing over 40 billion human antibody clones[J/OL]. PLoS One, 2014, 9(6): e100000[2025-07-20]. . |
| [40] | VALADON P, PÉREZ-TAPIA S M, NELSON R S, et al.. ALTHEA Gold Libraries™: antibody libraries for therapeutic antibody discovery[J]. mAbs, 2019, 11(3): 516-531. |
| [41] | FELLOUSE F A, BARTHELEMY P A, KELLEY R F, et al.. Tyrosine plays a dominant functional role in the paratope of a synthetic antibody derived from a four amino acid code[J]. J. Mol. Biol., 2006, 357(1): 100-114. |
| [42] | KOIDE A, GILBRETH R N, ESAKI K, et al.. High-affinity single-domain binding proteins with a binary-code interface[J]. Proc. Natl. Acad. Sci. USA, 2007, 104(16): 6632-6637. |
| [43] | ASHRAF M, FRIGOTTO L, SMITH M E, et al.. ProxiMAX randomization: a new technology for non-degenerate saturation mutagenesis of contiguous codons[J]. Biochem. Soc. Trans., 2013, 41(5): 1189-1194. |
| [44] | ECHEVERRI L M S, MORAES J C, DE LOURDES BORBA M M, et al.. Extended unpaired loop-oligonucleotide improves mutational rates in modified kunkel mutagenesis[J]. Int. J. Pept. Res. Ther., 2021, 27(1): 1-7. |
| [45] | HUANG R, FANG P, KAY B K. Improvements to the Kunkel mutagenesis protocol for constructing primary and secondary phage-display libraries[J]. Methods, 2012, 58(1): 10-17. |
| [46] | LIU B, LONG S, LIU J. Improving the mutagenesis efficiency of the Kunkel method by Codon optimization and annealing temperature adjustment[J]. N. Biotechnol., 2020, 56: 46-53. |
| [47] | VAN DEN BRULLE J, FISCHER M, LANGMANN T, et al.. A novel solid phase technology for high-throughput gene synthesis[J]. Biotechniques, 2008, 45(3): 340-343. |
| [48] | DUDGEON K, ROUET R, KOKMEIJER I, et al.. General strategy for the generation of human antibody variable domains with increased aggregation resistance[J]. Proc. Natl. Acad. Sci. USA, 2012, 109(27): 10879-10884. |
| [49] | MARUTHACHALAM B V, EL-SAYED A, LIU J, et al.. A single-framework synthetic antibody library containing a combination of canonical and variable complementarity-determining regions[J]. Chembiochem, 2017, 18(22): 2247-2259. |
| [50] | MARUTHACHALAM B V, BARRETO K, HOGAN D, et al.. Generation of synthetic antibody fragments with optimal complementarity determining region lengths for Notch-1 recognition[J/OL]. Front. Microbiol., 2022, 13: 931307[2025-07-20]. . |
| [51] | SCHULZ S, BOYER S, SMERLAK M, et al.. Parameters and determinants of responses to selection in antibody libraries[J/OL]. PLoS Comput. Biol., 2021, 17(3): e1008751[2025-07-20]. . |
| [52] | CHAN C E Z, CHAN A H Y, LIM A P C, et al.. Comparison of the efficiency of antibody selection from semi-synthetic scFv and non-immune Fab phage display libraries against protein targets for rapid development of diagnostic immunoassays[J]. J. Immunol. Methods, 2011, 373(1-2): 79-88. |
| [53] | O'CONNELL D, BECERRIL B, ROY-BURMAN A, et al.. Phage versus phagemid libraries for generation of human monoclonal antibodies[J]. J. Mol. Biol., 2002, 321(1): 49-56. |
| [54] | RONDOT S, KOCH J, BREITLING F, et al.. A helper phage to improve single-chain antibody presentation in phage display[J]. Nat. Biotechnol., 2001, 19(1): 75-78. |
| [55] | HOFER T, TANGKEANGSIRISIN W, KENNEDY M G, et al.. Chimeric rabbit/human Fab and IgG specific for members of the Nogo-66 receptor family selected for species cross-reactivity with an improved phage display vector[J]. J. Immunol. Methods, 2007, 318(1-2): 75-87. |
| [56] | FERRARA F, FANNI A, TEIXEIRA A A R, et al.. A next-generation Fab library platform directly yielding drug-like antibodies with high affinity, diversity, and developability[J/OL]. mAbs, 2024, 16(1): 2394230[2025-07-20]. . |
| [57] | WILSON H D, LI X, PENG H, et al.. A sortase a programmable phage display format for improved panning of Fab antibody libraries[J]. J. Mol. Biol., 2018, 430(21): 4387-4400. |
| [58] | BARRETO K, MARUTHACHALAM B V, HILL W, et al.. Next-generation sequencing-guided identification and reconstruction of antibody CDR combinations from phage selection outputs[J/OL]. Nucleic Acids Res., 2019, 47(9): e50[2025-07-20]. . |
| [59] | NOH J, KIM O, JUNG Y, et al.. High-throughput retrieval of physical DNA for NGS-identifiable clones in phage display library[J]. mAbs, 2019, 11(3): 532-545. |
| [60] | RAFTERY L J, HOWARD C B, GREWAL Y S, et al.. Retooling phage display with electrohydrodynamic nanomixing and nanopore sequencing[J]. Lab Chip, 2019, 19(24): 4083-4092. |
| [61] | LIU G, ZENG H, MUELLER J, et al.. Antibody complementarity determining region design using high-capacity machine learning[J]. Bioinformatics, 2020, 36(7): 2126-2133. |
| [62] | CHEN H, FAN X, ZHU S, et al.. Accurate prediction of CDR-H3 loop structures of antibodies with deep learning[J/OL]. eLife, 2024, 12: RP91512[2025-07-20]. . |
| [63] | RADWAŃSKA M J, JASKÓŁOWSKI M, DAVYDOVA E, et al.. The structure of the C-terminal domain of the nucleoprotein from the Bundibugyo strain of the Ebola virus in complex with a pan-specific synthetic Fab[J]. Acta Crystallogr. D Struct. Biol., 2018, 74(Pt 7): 681-689. |
| [64] | SLEZAK T, KOSSIAKOFF A A. Engineered ultra-high affinity synthetic antibodies for SARS-CoV-2 neutralization and detection[J/OL]. J. Mol. Biol., 2021, 433(10): 166956[2025-07-20]. . |
| [65] | KIM Y, LEE H, PARK K, et al.. Selection and characterization of monoclonal antibodies targeting middle east respiratory syndrome coronavirus through a human synthetic fab phage display library panning[J/OL]. Antibodies, 2019, 8(3): 42[2025-07-20]. . |
| [66] | BLAUVELT A, PAPP K A, GRIFFITHS C E M, et al.. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase Ⅲ, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial[J]. J. Am. Acad. Dermatol., 2017, 76(3): 405-417. |
| [67] | REICH K, ARMSTRONG A W, FOLEY P, et al.. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase Ⅲ, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial[J]. J. Am. Acad. Dermatol., 2017, 76(3): 418-431. |
| [68] | LACH-TRIFILIEFF E, MINETTI G C, SHEPPARD K, et al.. An antibody blocking activin type Ⅱ receptors induces strong skeletal muscle hypertrophy and protects from atrophy[J]. Mol. Cell. Biol., 2014, 34(4): 606-618. |
| [1] | Yaoxuan JIAO, Min LI, Xinya QU, Tianling LIU, Xiumei SHENG, Xiaoxiang ZHOU. Advances on Phage Genetic Engineering Technology and Applications [J]. Current Biotechnology, 2025, 15(2): 189-200. |
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