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Properties, production, and applications of camelid single-domain antibody fragments
Open accessAbstract
Camelids produce functional antibodies devoid of light chains of which the single N-terminal domain is fully capable of antigen binding. These single-domain antibody fragments (VHHs or Nanobodies®) have several advantages for biotechnological applications. They are well expressed in microorganisms and have a high stability and solubility. Furthermore, they are well suited for construction of larger molecules and selection systems such as phage, yeast, or ribosome display. This minireview offers an overview of (1) their properties as compared to conventional antibodies, (2) their production in microorganisms, with a focus on yeasts, and (3) their therapeutic applications.
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“Given their high-affinity, solubility and stability also in absence of the partner VL domain, the camelid VH domains (VHH) [4] and the shark VH domains called V-NAR (New Antigen Receptor) [5], are currently used as templates to generate highly efficient and stable new antibody fragments collectively termed nanobodies [6,7,8].”
From Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments (2020) · cites this paper as [4]
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Naturally occurring antibodies devoid of light chains
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“Sequence analysis (Hamers-Casterman et al. 1993; Muyldermans et al. 1994; Vu et al. 1997; Harmsen et al. 2000) and elucidation of the crystal structure (Desmyter et al.”
BackgroundInfluentialRapid generation of functional human IgG antibodies derived from Fab-on-phage display libraries
Jostock, T., Vanhove, M., Brepoels, E., van Gool, R., Daukandt, M., Wehnert, A., van Hegelsom, R., Dransfield, D., Sexton, D., Devlin, M., et al. (2004) · Journal of Immunological Methods · doi:10.1016/j.jim.2004.03.014 · Cited by 2,572
Engineered antibody fragments and the rise of single domains
Holliger, P., & Hudson, P. J. (2005) · Nature Biotechnology · doi:10.1038/nbt1142 · Cited by 1,928 · cited 1×
“As compared to human VH domains, the VHH FRs show a high sequence homology of more than 80%, and their 3D structures can be superimposed (Muyldermans et al. 2001; Holliger and Hudson 2005).”
BackgroundWard, E. S., Güssow, D., Griffiths, A. D., Jones, P., & Winter, G. P. (1989) · Nature · doi:10.1038/341544a0 · Cited by 1,010 · cited 2×
“Although isolated antibody heavy (Utsumi and Karush 1964) and light chains (Yoo et al. 1967) can retain antigenbinding specificity, their affinity and solubility is often reduced (Ward et al. 1989).”
BackgroundGreenberg, A. S., Avila, D. W., Hughes, M. K., Hughes, A. L., McKinney, E. C., & Flajnik, M. F. (1995) · Nature · doi:10.1038/374168a0 · Cited by 783 · cited 2×
“Although single-domain antibodies later were also identified in particular cartilaginous fish (Greenberg et al. 1995), most research on the biotechnological application of singledomain antibodies was done using camelids because of Appl Microbiol Biotechnol (2007) 77:13–22”
BackgroundSelection and identification of single domain antibody fragments from camel heavy‐chain antibodies
Ghahroudi, M. A., Desmyter, A., Wyns, L., HAMERS, R., & Muyldermans, S. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01062-4 · Cited by 775 · cited 1×
“Methods to isolate antigen-specific VHHs from immune ( Arbabi-Ghahroudi et al. 1997; Van der Linden et al. 2000a), nonimmune (Tanha et al. 2002; Yau et al. 2003; Verheesen et al. 2006), or semisynthetic (Goldman et al. 2006) libraries using phage, yeast, or ribosome display are now well established.”
BackgroundTargeting and tracing antigens in live cells with fluorescent nanobodies
Rothbauer, U., Zolghadr, K., Tillib, S. V., Nowak, D., Schermelleh, L., Gahl, A., Backmann, N., Conrath, K., Muyldermans, S., Cardoso, M. C., et al. (2006) · Nature Methods · doi:10.1038/nmeth953 · Cited by 715 · cited 1×
“Because of their stability, VHHs are especially suited for intrabody production because this requires expression in the reducing environment of the cytoplasm (Gueorguieva et al. 2006; Rothbauer et al. 2006).”
BackgroundMolecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies
Genst, E. D., Silence, K., Decanniere, K., Conrath, K., Loris, R., Kinne, J., Muyldermans, S., & Wyns, L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505379103 · Cited by 681 · cited 4×
“Occasionally, VHHs with affinity constants (KD) as low as 100 pM are isolated (Saerens et al. 2004; De Genst et al. 2006; Harmsen et al. 2006), which equals the affinity ceiling proposed for natural antibodies (Sundberg and Mariuzza 2002).”
BackgroundInfluentialSingle‐domain antibody fragments with high conformational stability
Dumoulin, M., Conrath, K., Meirhaeghe, A. V., Meersman, F., Heremans, K., Frenken, L. G. J., Muyldermans, S., Wyns, L., & Matagne, A. (2002) · Protein Science · doi:10.1110/ps.34602 · Cited by 641 · cited 4×
“VHHs are especially suited for oral immunotherapy because of their resistance against extremes of pH and the capacity to bind to the target at high concentrations of chaotropic agents (Dumoulin et al. 2002, 2003).”
BackgroundInfluentialStructure-Immunogenicity Relationships of Therapeutic Proteins
Hermeling, S., Crommelin, D. J. A., Schellekens, H., & Jiskoot, W. (2004) · Pharmaceutical Research · doi:10.1023/b:pham.0000029275.41323.a6 · Cited by 617 · cited 1×
“This could rely on their high sequence homology to conventional VH domains and on their high stability because aggregation of proteins is known to increase immunogenicity (Hermeling et al. 2004).”
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Single-domain antibody based thermally stable electrochemical immunosensor
Singh, A., Pasha, S. K., Manickam, P., & Bhansali, S. (2016) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2016.04.054 · Cited by 41
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“However, the development and use of bispeci fi c conventional antibody-based molecules has several limitations, including mispairing of heavy and lightchainsandinstability[15].”
InfluentialSingle Domain Antibodies as New Biomarker Detectors
Leow, C. H., Fischer, K., Leow, C. Y., Cheng, Q., Chuah, C., & McCarthy, J. S. (2017) · Diagnostics · doi:10.3390/diagnostics7040052 · Cited by 44
“of the heavy chain of HCAbs) or Nanobody® (Nb; Ablynx) [238].”
BackgroundMultimeric single-domain antibody complexes protect against bunyavirus infections
Schreur, P. J. W., van de Water, S., Harmsen, M. M., Bermúdez-Méndez, E., Drabek, D., Grosveld, F. G., Wernike, K., Beer, M., Aebischer, A., Daramola, O., et al. (2020) · eLife · doi:10.7554/elife.52716 · Cited by 42
Self-citationBacteriophages in health and disease
Hyman, P., & Abedon, S. T. (2012) · CABI eBooks · doi:10.1079/9781845939847.0000 · Cited by 41
A nanobody-based method for tracking factor XII activation in plasma
de Maat, S., van Dooremalen, S., de Groot, P. G., & Maas, C. (2013) · Thrombosis and Haemostasis · doi:10.1160/th12-11-0792 · Cited by 40
“Nanobodies are small enough to be efficiently produced in bacteria and are therefore useful for phage selection, genetic modification, and large-scale production (reviewed in [22]).”
BackgroundTintelnot, J., Baum, N., Schultheiß, C., Braig, F., Trentmann, M., Finter, J., Fumey, W., Bannas, P., Fehse, B., Riecken, K., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-0849 · Cited by 42
“Here, we provide evidence that the antigen-binding domain of heavy-chain-only antibodies from camelids (24), so-called nanobodies, may provide such desirable characteristics (25, 26).”
BackgroundApplications of nanobodies in plant science and biotechnology
Wang, W., Yuan, J., & Jiang, C. (2020) · Plant Molecular Biology · doi:10.1007/s11103-020-01082-z · Cited by 43
Kastelic, D., Frković‐Grazio, S., Baty, D., Truan, G., Komel, R., & Pompon, D. (2009) · Journal of Immunological Methods · doi:10.1016/j.jim.2009.08.016 · Cited by 40
Turner, K. B., Zabetakis, D., Goldman, E. R., & Anderson, G. P. (2014) · Protein Engineering Design and Selection · doi:10.1093/protein/gzu001 · Cited by 40
“…cryptic epitopes not accessible to conventional antibodies and their relative ease of expression and purification using Escherichia coli expression systems (Hamerscasterman et al., 1993; Greenberg et al., 1995; Harmsen and Haard, 2007; de Marco, 2011; Eyer and Hruska, 2012; Griffiths et al., 2013).”
BackgroundGhannam, A., Kumari, S., Muyldermans, S., & Abbady, A. Q. (2015) · Plant Molecular Biology · doi:10.1007/s11103-015-0282-5 · Cited by 44
COMBODY: one‐domain antibody multimer with improved avidity
Zhu, X., Wang, L., Liu, R., Flutter, B. R., Li, S., Ding, J., Tao, H., Liu, C., Sun, M., & Gao, B. (2010) · Immunology and Cell Biology · doi:10.1038/icb.2010.21 · Cited by 39
Kavanagh, O. V., Elliott, C. T., & Campbell, K. (2015) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-015-8502-z · Cited by 39
“For example sdAb paratopes have the ability to produce much longer H CDR3 regions than for other mammalian antibodies and these finger-like antigen-binding sites are conformationally constrained by additional interCDR disulfide bonds [19, 20].”
BackgroundTurner, K. B., Naciri, J. N., Liu, J. L., Anderson, G. P., Goldman, E. R., & Zabetakis, D. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149393 · Cited by 39
Terryn, S., Francart, A., Rommelaere, H., Stortelers, C., & Gucht, S. V. (2016) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0004902 · Cited by 39
Anti-VP6 VHH: An Experimental Treatment for Rotavirus A-Associated Disease
Maffey, L., Vega, C. G., Miño, S., Garaicoechea, L., & Parreño, V. G. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162351 · Cited by 39
“VHH are also resistant to other denaturing conditions, such as extreme pH [23,39] and high urea concentrations [41].”
BackgroundIdentification and characterization of Nanobodies targeting the EphA4 receptor
Schoonaert, L., Rué, L., Roucourt, B., Timmers, M., Little, S., Chávez‐Gutiérrez, L., Dewilde, M., Joyce, P. I., Curnock, A. P., Weber, P., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.774141 · Cited by 38
Novel half‐life extended anti‐MIF nanobodies protect against endotoxic shock
Sparkes, A., BAETSELIER, P. D., Brys, L., Cabrito, I., Sterckx, Y. G. ‐., Schoonooghe, S., Muyldermans, S., Raes, G., Bucala, R., Vanlandschoot, P., et al. (2018) · The FASEB Journal · doi:10.1096/fj.201701189r · Cited by 39
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A resource of high-quality and versatile nanobodies for drug delivery
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Therapeutic Monoclonal Antibodies: Past, Present, and Future
Strohl, W. R. (2009) · Wiley eBooks · doi:10.1002/9780470485408.ch1 · Cited by 40
Nanobody-based magnetic chemiluminescence immunoassay for one-pot detection of ochratoxin A
Zuo, H., Wang, X., Liu, W., Chen, Z., Liu, R., Yang, H. N., Xia, C., Xie, J., Sun, T., & Ning, B. (2023) · Talanta · doi:10.1016/j.talanta.2023.124388 · Cited by 38
Fusion of an F c chain to a VHH boosts the accumulation levels in A rabidopsis seeds
Buck, S. D., Nolf, J., Meyer, T. D., Virdi, V., Wilde, K. D., Lerberge, E. V., Droogenbroeck, B. V., & Depicker, A. (2013) · Plant Biotechnology Journal · doi:10.1111/pbi.12094 · Cited by 38
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Schönberger, T., Fandrey, J., & Prost-Fingerle, K. (2021) · Cancers · doi:10.3390/cancers13010159 · Cited by 39
Immunotoxins and nanobody-based immunotoxins: review and update
Khirehgesh, M. R., Sharifi, J., Safari, F., & Akbari, B. (2021) · Journal of drug targeting · doi:10.1080/1061186x.2021.1894435 · Cited by 41
Tanaka, Y., Kawanishi, M., Nakanishi, M., Yamasaki, H., & Takeuchi, T. (2022) · Modern Rheumatology · doi:10.1093/mr/roac119 · Cited by 38
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McCafferty, J., & Schofield, D. J. (2015) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2015.01.003 · Cited by 37
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“lactis) significantly reduced inflammation in dextran sulfate sodiuminduced chronic colitis mice (61).”
del Río, B., Redruello, B., Fernández, M., Martín, M. C., Ladero, V., & Álvarez, M. A. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.03179 · Cited by 37
VHH-Photosensitizer Conjugates for Targeted Photodynamic Therapy of Met-Overexpressing Tumor Cells
Heukers, R., Mashayekhi, V., Ramirez-Escudero, M., de Haard, H., Verrips, T. C., Henegouwen, P. M. P. V. B. E., & Oliveira, S. (2019) · Antibodies · doi:10.3390/antib8020026 · Cited by 39
“These features favor the selection and production process and make VHHs very stable [11].”
Abbady, A. Q., Al-Daoude, A., Al-Mariri, A., Zarkawi, M., & Muyldermans, S. (2012) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2012.01.015 · Cited by 37
NANOBODY® Molecule, a Giga Medical Tool in Nanodimensions
Kunz, S., Durandy, M., Seguin, L., & Féral, C. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713229 · Cited by 36
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Kiefer, J. D., & Neri, D. (2016) · Immunological Reviews · doi:10.1111/imr.12391 · Cited by 37
“Obviously, bispecific molecules could also be generated by the tandem arrangements of other antibody-like fragments, such as VHH domains of camelid antibodies (95) or other types of globular-binding domains (96).”
BackgroundKazemi‐Lomedasht, F., Muyldermans, S., Habibi‐Anbouhi, M., & Behdani, M. (2018) · PubMed Central · doi:10.22038/ijbms.2018.24898.6183 · Cited by 36
“such as Fab, Fv and single-chain variable fragment (scFv) (6-9).”
Abderrazek, R. B., Vincke, C., Hmila, I., Saerens, D., Abidi, N., Ayeb, M. E., Muyldermans, S., & Bouhaouala‐Zahar, B. (2011) · Protein Engineering Design and Selection · doi:10.1093/protein/gzr037 · Cited by 39
Palomo, C., Más, V., Detalle, L., Depla, E., Cano, O., Vázquez, M., Stortelers, C., & Melero, J. A. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00842-16 · Cited by 35
“Compared to conventional antibodies, Nanobodies are intrinsically stable molecules with improved solubility (40) and have the capacity to be nebulized without loss of physico-chemical properties or of potency (41).”
BackgroundPandey, N., Mandal, M., Samanta, D., Mukherjee, G., & Dutta, G. (2023) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2023.115733 · Cited by 36
Park, S. R., Lee, J. H., Kim, K., Kim, T. M., Lee, S. H., Choo, Y., Kim, K. S., & Ko, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041354 · Cited by 35
“Various forms of antibodies, including full size, ScFv, minibody, and camelid, have been modified and expressed in heterologous biosystems [13].”
BackgroundNanobody–siRNA Conjugates for Targeted Delivery of siRNA to Cancer Cells
Zavoiura, O., Brunner, B., Casteels, P., Zimmermann, L. T., Ozog, M., Boutton, C., Helms, M. W., Wagenaar, T. R., Adam, V., Peterka, J., et al. (2021) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c01001 · Cited by 36
Antibody engineering and its therapeutic applications
Kandari, D., & Bhatnagar, R. (2021) · International Reviews of Immunology · doi:10.1080/08830185.2021.1960986 · Cited by 36
Single Domain Antibody application in bacterial infection diagnosis and neutralization
Qin, Q., Liu, H., He, W., Guo, Y., Zhang, J., She, J., Zheng, F., Zhang, S., Muyldermans, S., & Wen, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1014377 · Cited by 35
Ezzine, A., M’hirsi, S., Bouhaouala‐Zahar, B., Hmila, I., Baciou, L., & Marzouki, M. N. (2012) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.67 · Cited by 35
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“A high fraction are extremely stable, can fold correctly under a wide range of conditions, and are being tested as gene and protein therapeutics [16, 17].”
BackgroundVandesquille, M., Li, T., Po, C., Ganneau, C., Lenormand, P., Dudeffant, C., Czech, C., Grueninger, F., Duyckaerts, C. J., Delatour, B., et al. (2017) · mAbs · doi:10.1080/19420862.2017.1342914 · Cited by 34
“They are very stable, highly specific for the target antigen, and they bind epitopes not recognized by conventional antibodies.(20-22) Their small size (hydrodynamic radius of 2-2.”
BackgroundNanobodies and Cancer: Current Status and New Perspectives
Allegra, A., Innao, V., Gerace, D. G., Vaddinelli, D., Allegra, A. G., & Musolino, C. (2018) · Cancer Investigation · doi:10.1080/07357907.2018.1458858 · Cited by 34
Single domain antibodies in the development of immunosensors for diagnostics
Bastos-Soares, E. A., Sousa, R. M. O., Gómez, A. F., Alfonso, J., Kayano, A. M., Zanchi, F. B., Funes‐Huacca, M. E., Stábeli, R. G., Soares, A. M., Pereira, S. D. S., et al. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.10.031 · Cited by 35
Леонидовна, Т. И., Sedova, E. S., Gribova, I. Y., Ivanova, T. I., Vasilev, L. A., Rutovskaya, M. V., Lysenko, A. A., Шмаров, М. М., Logunov, D. Y., Naroditsky, B. S., et al. (2012) · Antiviral Research · doi:10.1016/j.antiviral.2012.12.021 · Cited by 34
Therapeutic potential of Camel Milk
Dubey, U. S., Lal, M., Mittal, A., & Kapur, S. (2015) · Emirates Journal of Food and Agriculture · doi:10.9755/ejfa.2015-04-122 · Cited by 35
Nanobody-Based EGFR-Targeting Immunotoxins for Colorectal Cancer Treatment
Narbona, J., Hernández-Baraza, L., Gordo, R. G., Sanz, L., & Lacadena, J. (2023) · Biomolecules · doi:10.3390/biom13071042 · Cited by 32
Franco, E. J., Sonneson, G. J., DeLegge, T. J., Hofstetter, H., Horn, J. R., & Hofstetter, O. (2009) · Journal of Chromatography B · doi:10.1016/j.jchromb.2009.06.017 · Cited by 33
Promises and Challenges of the Type Three Secretion System Injectisome as an Antivirulence Target
Fasciano, A. C., Shaban, L., & Mecsas, J. C. (2019) · EcoSal Plus · doi:10.1128/ecosalplus.esp-0032-2018 · Cited by 33
“Single-domain antibodies that consist of the N-terminal variable region of an immunoglobulin heavy chain (VHH) but not the light chain can be isolated from camelid species (65).”
BackgroundGransagne, M., Aymé, G., Brier, S., Friec, G. C.-L., Mériaux, V., Nowakowski, M., Déjardin, F., Levallois, S., de Melo, G. D., Donati, F., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101290 · Cited by 33
“VHHs have been raised against numerous viruses (reviewed in (22, 23)) includingHIV (24, 25); influenzaA (26–28); rabies virus (26); poliovirus (29); foot andmouth disease virus (30); Rotavirus (31), hepatitis C virus (32), and against SARS-CoV-1, MERSCoV, and SARS-CoV-2 spike proteins (33–37).”
BackgroundProduction of Novel VHH Nanobody Inhibiting Angiogenesis by Targeting Binding Site of VEGF
Ebrahimizadeh, W., Gargari, S. L. M., Javidan, Z., & Rajabibazl, M. (2015) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-015-1695-y · Cited by 33
“In addition to low molecular mass, nanobodies possess many inherent favorable characteristics, such as high physiochemical stability, better tissue penetration, rapid clearance, and high expression in yeasts and bacteria [16].”
BackgroundOkazaki, F., Aoki, J.-I., Tabuchi, S., Tanaka, T., Ogino, C., & Kondo, A. (2012) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-012-4158-1 · Cited by 33
“The discovery of a class of camelid antibodies (including camels and llamas) that lack light chains has provided a biological example wherein antigen recognition is reduced to a single domain (Hamers-Casterman et al. 1993).”
BackgroundModular DNA origami–based electrochemical detection of DNA and proteins
Jeon, B.-J., Guareschi, M. M., Stewart, J. M., Wu, E., Gopinath, A., Arroyo‐Currás, N., Dauphin‐Ducharme, P., Plaxco, K. W., Lukeman, P. S., & Rothemund, P. W. K. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2311279121 · Cited by 32
“Conjugating oligos to other binder classes such as antibodies, antibody fragments(91), nanobodies(54), or peptides(92) will allow for their facile incorporation into the lily pad.”
Production of Nanobodies against Prostate-Specific Membrane Antigen (PSMA) Recognizing LnCaP Cells
Zare, H., Rajabibazl, M., Rasooli, I., Ebrahimizadeh, W., Bakherad, H., Ardekani, L. S., & Gargari, S. L. M. (2014) · The International Journal of Biological Markers · doi:10.5301/jbm.5000063 · Cited by 32
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Self-citationHarmsen, M. M., Fijten, H., Dekker, A., & Eblé, P. L. (2008) · Veterinary Microbiology · doi:10.1016/j.vetmic.2008.04.030 · Cited by 32
Self-citationUtilizing nanobody technology to target non-immunodominant domains of VAR2CSA
Ditlev, S. B., Florea, R., Nielsen, M. A., Theander, T. G., Magez, S., Boeuf, P., & Salanti, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084981 · Cited by 31
“The CDR regions of Nbs are often longer and more flexible than corresponding regions of conventional antibodies and thus can bind epitopes that physically cannot be targeted by conventional immunoglobulins [28,31,32].”
Use of camel single-domain antibodies for the diagnosis and treatment of zoonotic diseases
Lafaye, P. J., & Li, T. (2018) · Comparative Immunology Microbiology and Infectious Diseases · doi:10.1016/j.cimid.2018.09.009 · Cited by 30
“They can thus be easily engineered, cloned, and expressed with high yields using various expression systems [15] .”
BackgroundSelection and characterization of protective anti-chikungunya virus single domain antibodies
Liu, J. L., Shriver‐Lake, L. C., Zabetakis, D., Anderson, G. P., & Goldman, E. R. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.11.016 · Cited by 32
Hassani, M., Taheri, F. H., Sharifzadeh, Z., Arashkia, A., Hadjati, J., van Weerden, W. M., Abdoli, S., Modarressi, M. H., & Abolhassani, M. (2019) · Iranian Biomedical Journal · doi:10.29252/ibj.24.2.81 · Cited by 34
Nanobodies as Versatile Tool for Multiscale Imaging Modalities
Erreni, M., Schorn, T., D’Autilia, F., & Doni, A. (2020) · Biomolecules · doi:10.3390/biom10121695 · Cited by 29
“A variety of methods are currently available for the production of Nbs, generally involving the generation of a Nb library and the following selection of the best candidates [49,50].”
MethodNanobody-armed T cells endow CAR-T cells with cytotoxicity against lymphoma cells
Wang, H., Wang, L., Li, Y., Li, G., Zhang, X., Jiang, D., Zhang, Y.-T. Y., Liu, L., Chu, Y., & Xu, G. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02151-z · Cited by 31
“In addition, most sequences with identity to the human VH gene family III result in weak immunogenicity, therefore, applying Nb as part of the antibody recognition of CAR-T cells may be safer than mAbs derived from mice [27].”
BackgroundNguyen-Duc, T., Peeters, E., Muyldermans, S., Charlier, D., & Hassanzadeh‐Ghassabeh, G. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1342 · Cited by 33
Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics
Ou, L., Setegne, M. T., Elliot, J., Shen, F., & Dassama, L. M. K. (2025) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00595 · Cited by 33
Kandalaft, H., Hussack, G., Aubry, A. J., van Faassen, H., Guan, Y., Arbabi‐Ghahroudi, M., MacKenzie, R., Logan, S. M., & Tanha, J. (2015) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-015-6594-1 · Cited by 30
High‐throughput mAb expression and purification platform based on transient CHO
Barnard, G. C., Hougland, M. D., & Rajendra, Y. (2014) · Biotechnology Progress · doi:10.1002/btpr.2012 · Cited by 30
Construction and expression of an anti-VEGFR2 Nanobody-Fc fusionbody in NS0 host cell
Qasemi, M., Behdani, M., Shokrgozar, M. A., Kazemiha, V. M., Mohseni-Kuchesfahani, H., & Habibi‐Anbouhi, M. (2016) · Protein Expression and Purification · doi:10.1016/j.pep.2016.03.004 · Cited by 30
Selection of Non-aggregating VH Binders from Synthetic VH Phage-Display Libraries
Arbabi‐Ghahroudi, M., MacKenzie, R., & Tanha, J. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-554-1_10 · Cited by 30
Khodabakhsh, F., Norouzian, D., Vaziri, B., Cohan, R. A., Sardari, S., Mahboudi, F., Behdani, M., Mansouri, K., & Mehdizadeh, A. (2017) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2017.1369426 · Cited by 30
“In addition, nanobodies can recognize hidden antigenic sites that normally are not detectable by whole antibodies [7].”
BackgroundLuiz, M. B., Pereira, S. D. S., Prado, N. D. R., Gonçalves, N., Kayano, A. M., Moreira-Dill, L. S., Sobrinho, J. C., Zanchi, F. B., Fuly, A. L., Fernandes, C. D. F., et al. (2018) · Toxins · doi:10.3390/toxins10040142 · Cited by 32
Engineering Bacillus subtilis as a Versatile and Stable Platform for Production of Nanobodies
Yang, M., Zhu, G., Korza, G., Sun, X., Setlow, P., & Li, J. (2020) · Applied and Environmental Microbiology · doi:10.1128/aem.02938-19 · Cited by 30
“Nbs have small sizes (12 to 17 kDa), high solubility, and high thermal stability compared to conventional antibodies (8, 9).”
BackgroundAnti-Idiotypic Agonistic Antibodies: Candidates for the Role of Universal Remedy
Stanova, A. K., Ryabkova, V. A., Tillib, S. V., Utekhin, V. J., Churilov, L. P., & Shoenfeld, Y. (2020) · Antibodies · doi:10.3390/antib9020019 · Cited by 30
“We also suggest that the discovery of single-domain antibody fragments (VHHs or Nanobodies®) with a high stability and solubility in camelids, which already have certain therapeutic applications [94,95], would alleviate the difficulties in the production of anti-IDs for the treatment of various human diseases.”
BackgroundDevelopment of a nanobody-based immunoassay for the sensitive detection of fibrinogen-like protein 1
Zhang, W., Liu, T., Wu, M., Chen, X., Li, H., Shi, Z., Li, Y., Li, X.-Y., Xu, H., Gong, L., et al. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00574-4 · Cited by 31
Improving the yield of recalcitrant Nanobodies® by simple modifications to the standard protocol
Kariuki, C. K., & Magez, S. (2021) · Protein Expression and Purification · doi:10.1016/j.pep.2021.105906 · Cited by 29
Lentz, E. M., Garaicoechea, L., Alfano, E. F., Parreño, V. G., Wigdorovitz, A., & Bravo-Almonacid, F. F. (2012) · Planta · doi:10.1007/s00425-012-1642-x · Cited by 30
Stamova, S., Koristka, S., Keil, J., Arndt, C., Feldmann, A., Michalk, I., Bartsch, H., Bippes, C. C., Schmitz, M., Cartellieri, M., et al. (2012) · Antibodies · doi:10.3390/antib1020172 · Cited by 30
Botulinum Neurotoxins and Botulism: A Novel Therapeutic Approach
Thanongsaksrikul, J., & Chaicumpa, W. (2011) · Toxins · doi:10.3390/toxins3050469 · Cited by 30
“The safety should be due to the high degree of sequence homology between human VH and camel VHH immunoglobulin frameworks (FRs) which is >80% [111].”
BackgroundRousserie, G., Grinevich, R., Brazhnik, K., Even-Desrumeaux, K., Réveil, B., Tabary, T., Chames, P., Baty, D., Cohen, J. H. M., Nabiev, I. R., et al. (2015) · Analytical Biochemistry · doi:10.1016/j.ab.2015.02.029 · Cited by 29
Structural Effects of Two Camelid Nanobodies Directed to Distinct C-Terminal Epitopes on α-Synuclein
El-Turk, F., Newby, F. N., Genst, E. D., Guilliams, T., Sprules, T. J., Mittermaier, A., Dobson, C. M., & Vendruscolo, M. (2016) · Biochemistry · doi:10.1021/acs.biochem.6b00149 · Cited by 29
Diverse human VH antibody fragments with bio-therapeutic properties from the Crescendo Mouse
Teng, Y., Young, J. L., Edwards, B. M., Hayes, P., Thompson, L., Johnston, C. M., Edwards, C., Sanders, Y., Writer, M. J., Pinto, D., et al. (2019) · New Biotechnology · doi:10.1016/j.nbt.2019.10.003 · Cited by 30
Marturano, A., Hendrickx, M. L. V., Falcinelli, E., Sebastiano, M., Guglielmini, G., Hassanzadeh‐Ghassabeh, G., Muyldermans, S., Declerck, P. J., & Gresele, P. (2019) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2019.102103 · Cited by 30
Ferrari, D., Garrapa, V., Locatelli, M., & Bolchi, A. (2019) · Molecular Biotechnology · doi:10.1007/s12033-019-00224-z · Cited by 29
Zdechlik, A. C., He, Y., Aird, E. J., Gordon, W. R., & Schmidt, D. (2019) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.9b00790 · Cited by 30
Development of a Humanized VHH Based Recombinant Antibody Targeting Claudin 18.2 Positive Cancers
Zhong, W., Lu, Y., Ma, Z., He, Y., Ding, Y., Yao, G., Zhou, Z., Dong, J., Fang, Y., Jiang, W., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.885424 · Cited by 29
“Additionally, fusions of targeting VHHs to human IgG1 Fc can be used to recruit effector functions of ADCC and CDC (33).”
BackgroundInfluentialMolecular Imprint of Enzyme Active Site by Camel Nanobodies
Li, J., Xia, L., Su, Y., Liu, H., Xia, X., Lu, Q., Yang, C., & Reheman, K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.336370 · Cited by 29
Creation of a gated antibody as a conditionally functional synthetic protein
Gunnoo, S. B., Finney, H. M., BAKER, T. S., Lawson, A. D. G., Anthony, D. C., & Davis, B. G. (2014) · Nature Communications · doi:10.1038/ncomms5388 · Cited by 29
Survey of the camel urinary proteome by shotgun proteomics using a multiple database search strategy
Alhaider, A. A., Bayoumy, N. M. K., Argo, E., Gader, A. G. M. A., & Stead, D. (2012) · PROTEOMICS · doi:10.1002/pmic.201100631 · Cited by 28
Nanobodies: A New Approach for the Diagnosis and Treatment of Viral Infectious Diseases
Sroga, P., Safronetz, D., & Stein, D. R. (2020) · Future Virology · doi:10.2217/fvl-2019-0167 · Cited by 29
Shin, C., Kim, S. S., & Jo, Y. H. (2021) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2021.08.005 · Cited by 27
Adenovirus-Derived Vectors for Prostate Cancer Gene Therapy
de Vrij, J., Willemsen, R. A., Lindholm, L., & Hoeben, R. C. (2009) · Human Gene Therapy · doi:10.1089/hum.2009.203 · Cited by 28
“Camelid and human single-domain antibody fragments may be applicable in a similar manner (Harmsen and De Haard, 2007).”
Monegal, A., Olichon, A., Béry, N., Filleron, T., Favre, G., & de Marco, A. (2011) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2011.06.016 · Cited by 29
“%) of variable single domains that seem to originate from VH germline genes have been repeatedly identified together with canonical VHHs in immune libraries (Saerens et al., 2004; Harmsen and De Haard, 2007).”
BackgroundDecaf and the Steeplechase Towards Decaffito—the Coffee from Caffeine-Free Arabica Plants
Mazzafera, P., Baumann, T. W., Shimizu, M. M., & Silvarolla, M. B. (2009) · Tropical Plant Biology · doi:10.1007/s12042-009-9032-7 · Cited by 28
“Lately, a heat (<90°C) stable caffeine antibody was produced from camelids [67, 83].”
Metadata
- Authors
- Harmsen, M. M., & De Haard, H. J.
- Affiliations
- Wageningen University & Research (NL)
- Ablynx (Belgium) (BE)
- Corresponding author
- Harmsen, M. M.
- Venue
- Applied Microbiology and Biotechnology
- Published
- 2007-08-18
- Volume
- 77
- Issue
- 1
- Pages
- 13-22
- ISSN
- 0175-7598 (ISSN-L)
- 1432-0614
- PMC
- PMC2039825
- OpenAlex
- W2147451568
- Cited by
- 809
- References
- 96
- Citations by year
- 2026: 31 · 2025: 43 · 2024: 48 · 2023: 41 · 2022: 41 · 2021: 65 · 2020: 57 · 2019: 49 · 2018: 53 · 2017: 42 · 2016: 46 · 2015: 48 · 2014: 53 · 2013: 40 · 2012: 52
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Applied Microbiology and Biotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Agricultural and Biological Sciences › Food Science › Animal Diversity and Health Studies
- Keywords
- single-domain antibody fragments, VHH, nanobodies, camelid antibodies, recombinant antibody production, yeast expression system, phage display, ribosome display, yeast surface display, therapeutic applications
- MeSH terms
- Animals, Camelids, New World, Immunoglobulin Fragments, Immunoglobulin Heavy Chains, Models, Biological
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