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Therapeutic protein aggregation: mechanisms, design, and control

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Roberts, Christopher J.·2014·Trends in Biotechnology

DOI 10.1016/j.tibtech.2014.05.005PMC PMC4146573

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Abstract

Although it is well known that proteins are only marginally stable in their folded states, it is often less well appreciated that most proteins are inherently aggregation-prone in their unfolded or partially unfolded states, and the resulting aggregates can be extremely stable and long-lived. For therapeutic proteins, aggregates are a significant risk factor for deleterious immune responses in patients, and can form via a variety of mechanisms. Controlling aggregation using a mechanistic approach may allow improved design of therapeutic protein stability, as a complement to existing design strategies that target desired protein structures and function. Recent results highlight the importance of balancing protein environment with the inherent aggregation propensities of polypeptide chains.

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Intermolecular and Surface Forces
(2011) · Elsevier eBooks · doi:10.1016/b978-0-12-391927-4.10024-6 · Cited by 17,242
Protein Folding
Creighton, T. E. (1992) · Cited by 1,583
Effects of protein aggregates: An immunologic perspective
Rosenberg, A. S. (2006) · The AAPS Journal · doi:10.1208/aapsj080359 · Cited by 1,355
Protein aggregation: folding aggregates, inclusion bodies and amyloid
Fink, A. L. (1998) · Folding and Design · doi:10.1016/s1359-0278(98)00002-9 · Cited by 1,179
Rationalization of the effects of mutations on peptide andprotein aggregation rates
Chiti, F., Stefani, M., Taddei, N., Ramponi, G., & Dobson, C. M. (2003) · Nature · doi:10.1038/nature01891 · Cited by 1,072
Protein aggregation and its inhibition in biopharmaceutics
Wang, W. (2005) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2004.11.014 · Cited by 1,023
Antibody Structure, Instability, and Formulation
Wang, W., Singh, S. K., Zeng, D. L., King, K., & Nema, S. (2006) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20727 · Cited by 948
The immunogenicity of humanized and fully human antibodies
Harding, F., Stickler, M. M., Razo, J., & DuBridge, R. B. (2010) · mAbs · doi:10.4161/mabs.2.3.11641 · Cited by 743
Protein aggregation kinetics, mechanism, and curve-fitting: A review of the literature
Morris, A. M., Watzky, M. A., & Finke, R. G. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2008.10.016 · Cited by 693
Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity
Boder, E. T., Midelfort, K. S., & Wittrup, K. D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.170297297 · Cited by 673
Structure-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
Stability engineering of antibody single-chain Fv fragments
Wörn, A., & Plückthun, A. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4265 · Cited by 616
Design of therapeutic proteins with enhanced stability
Chennamsetty, N., Voynov, V., Kayser, V., Helk, B., & Trout, B. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904191106 · Cited by 605
Overlooking Subvisible Particles in Therapeutic Protein Products: Gaps That May Compromise Product Quality
Carpenter, J. F., Randolph, T. W., Jiskoot, W., Crommelin, D. J. A., Middaugh, C. R., Winter, G., Fan, Y., Kirshner, S., Verthelyi, D. I., Kozlowski, S., et al. (2008) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21530 · Cited by 600
[17] Analysis of protein aggregation kinetics
Ferrone, F. A. (1999) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(99)09019-9 · Cited by 547
Introduction to protein crystallization
McPherson, A., & Gavira, J. A. (2013) · Acta Crystallographica Section F Structural Biology Communications · doi:10.1107/s2053230x13033141 · Cited by 545
The development of stable protein formulations: a close look at protein aggregation, deamidation, and oxidation.
Cleland, J. L., Powell, M., & Shire, S. J. (1993) · PubMed · Cited by 541
Kinetic theory of fibrillogenesis of amyloid β-protein
Lomakin, A., Teplow, D. B., Kirschner, D. A., & Benedek, G. B. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.7942 · Cited by 529
Predicting the energetics of osmolyte-induced protein folding/unfolding
Auton, M. T., & Bolen, D. W. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507053102 · Cited by 431
Shaken, Not Stirred: Mechanical Stress Testing of an IgG1 Antibody
Kiese, S., Pappenberger, A., Frieß, W., & Mahler, H. (2008) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21328 · Cited by 398
An Industry Perspective on the Monitoring of Subvisible Particles as a Quality Attribute for Protein Therapeutics
Singh, S. K., Afonina, N., Awwad, M., Bechtold-Peters, K., Blue, J. T., Chou, D. K., Cromwell, M. E. M., Krause, H.-J., Mahler, H., Meyer, B. K., et al. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22097 · Cited by 337
Fragmentation of monoclonal antibodies
Vlasak, J., & Ionescu, R. M. (2011) · mAbs · doi:10.4161/mabs.3.3.15608 · Cited by 335
Non‐native protein aggregation kinetics
Roberts, C. J. (2007) · Biotechnology and Bioengineering · doi:10.1002/bit.21627 · Cited by 335
Self-citation
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Weiss, W. F., Young, T. M., & Roberts, C. J. (2008) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21521 · Cited by 316
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Joubert, M. K., Hokom, M. M., Eakin, C. M., Zhou, L., Deshpande, M., Baker, M., Goletz, T. J., Kerwin, B. A., Chirmule, N., Narhi, L. O., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.330902 · Cited by 268
What's fueling the biotech engine—2012 to 2013
Aggarwal, S. (2014) · Nature Biotechnology · doi:10.1038/nbt.2794 · Cited by 254
Protein Instability and Immunogenicity: Roadblocks to Clinical Application of Injectable Protein Delivery Systems for Sustained Release
Jiskoot, W., Randolph, T. W., Volkin, D. B., Middaugh, C. R., Schöneich, C., Winter, G., Frieß, W., Crommelin, D. J. A., & Carpenter, J. F. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23018 · Cited by 251
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Şahin, E., Grillo, A. O., Perkins, M. D., & Roberts, C. J. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22198 · Cited by 247
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Philo, J. S. (2006) · The AAPS Journal · doi:10.1208/aapsj080365 · Cited by 245
Aggregation of Therapeutic Proteins
Wang, W., & Roberts, C. J. (2010) · Wiley eBooks · doi:10.1002/9780470769829 · Cited by 235
Effect of tween 20 on freeze-thawing- and agitation-induced aggregation of recombinant human factor XIII
Krielgaard, L., Jones, L. S., Randolph, T. W., Frøkjær, S., Flink, J. M., Manning, M. C., & Carpenter, J. F. (1998) · Journal of Pharmaceutical Sciences · doi:10.1021/js980126i · Cited by 232
The Kinetics of Nucleated Polymerizations at High Concentrations: Amyloid Fibril Formation Near and Above the “Supercritical Concentration”
Powers, E. T., & Powers, D. L. (2006) · Biophysical Journal · doi:10.1529/biophysj.105.073767 · Cited by 212
A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties
Tiller, T., Schuster, I., Deppe, D., Siegers, K., Strohner, R., Herrmann, T., Berenguer, M., Poujol, D., Stehle, J., Stark, Y., et al. (2013) · mAbs · doi:10.4161/mabs.24218 · Cited by 209
Chemical Modifications in Therapeutic Protein Aggregates Generated under Different Stress Conditions
Luo, Q., Joubert, M. K., Stevenson, R., Ketchem, R. R., Narhi, L. O., & Wypych, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.160440 · Cited by 204
Potential aggregation prone regions in biotherapeutics: A survey of commercial monoclonal antibodies
Wang, X., Das, T. K., Singh, S. K., & Kumar, S. (2009) · mAbs · doi:10.4161/mabs.1.3.8035 · Cited by 198
General strategy for the generation of human antibody variable domains with increased aggregation resistance
Dudgeon, K., Rouet, R., Kokmeijer, I., Schofield, P., Stolp, J., Langley, D. B., Stock, D., & Christ, D. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202866109 · Cited by 191
Protein engineering of enzymes for process applications
Woodley, J. M. (2013) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2013.03.017 · Cited by 182
Structural thermodynamics of protein preferential solvation: Osmolyte solvation of proteins, aminoacids, and peptides
Auton, M. T., Bolen, D. W., & Rösgen, J. (2008) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22103 · Cited by 176
Kinetics of Irreversible Protein Aggregation: Analysis of Extended Lumry−Eyring Models and Implications for Predicting Protein Shelf Life
Roberts, C. J. (2003) · The Journal of Physical Chemistry B · doi:10.1021/jp026827s · Cited by 159
Self-citation
2011 FDA drug approvals
Mullard, A. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3657 · Cited by 156
Elucidation of Acid-induced Unfolding and Aggregation of Human Immunoglobulin IgG1 and IgG2 Fc
Latypov, R. F., Hogan, S., Lau, H., Gadgil, H. S., & Liu, D. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.297697 · Cited by 152
Structure-Based Design of Supercharged, Highly Thermoresistant Antibodies
Miklos, A. E., Kluwe, C., Der, B. S., Pai, S., Sircar, A., Hughes, R. A., Berrondo, M., Xu, J., Codrea, V., Buckley, P. E., et al. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.01.018 · Cited by 142
Different Equilibrium Stability Behavior of ScFv Fragments: Identification, Classification, and Improvement by Protein Engineering
Wörn, A., & Plückthun, A. (1999) · Biochemistry · doi:10.1021/bi9902079 · Cited by 140
Acid-Induced Aggregation of Human Monoclonal IgG1 and IgG2: Molecular Mechanism and the Effect of Solution Composition
Hari, S. B., Lau, H., Razinkov, V. I., Chen, S., & Latypov, R. F. (2010) · Biochemistry · doi:10.1021/bi100841u · Cited by 139
Computational models for the prediction of polypeptide aggregation propensity
Caflisch, A. (2006) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2006.07.009 · Cited by 130
Nonnative Aggregation of an IgG1 Antibody in Acidic Conditions: Part 1. Unfolding, Colloidal Interactions, and Formation of High-Molecular-Weight Aggregates
Brummitt, R. K., Nesta, D. P., Chang, L., Chase, S. F., Laue, T. M., & Roberts, C. J. (2011) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.22448 · Cited by 125
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Arosio, P., Rima, S., & Morbidelli, M. (2012) · Pharmaceutical Research · doi:10.1007/s11095-012-0885-3 · Cited by 123
Glutamine Deamidation Destabilizes Human γD-Crystallin and Lowers the Kinetic Barrier to Unfolding
Flaugh, S. L., Mills-Henry, I., & King, J. W. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603882200 · Cited by 117
Rational design of aggregation-resistant bioactive peptides: Reengineering human calcitonin
Fowler, S. A., Poon, S., Muff, R., Chiti, F., Dobson, C. M., & Zurdo, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501215102 · Cited by 114
Aggregation of a monoclonal antibody induced by adsorption to stainless steel
Bee, J. S., Davis, M., Freund, E., Carpenter, J. F., & Randolph, T. W. (2009) · Biotechnology and Bioengineering · doi:10.1002/bit.22525 · Cited by 113
Thermodynamically Stable Aggregation-Resistant Antibody Domains through Directed Evolution
Famm, K., Hansen, L., Christ, D., & Winter, G. P. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.10.075 · Cited by 109
Theoretical Approaches to Protein Aggregation
Gsponer, J., & Vendruscolo, M. (2006) · Protein and Peptide Letters · doi:10.2174/092986606775338407 · Cited by 107
Aggregation of therapeutic proteins
Wang, W., & Roberts, C. J. (2010) · Wiley eBooks · Cited by 104
Self-citation
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Flaugh, S. L., Kosinski‐Collins, M. S., & King, J. (2005) · Protein Science · doi:10.1110/ps.051460505 · Cited by 104
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Flaugh, S. L., Kosinski‐Collins, M. S., & King, J. W. (2005) · Protein Science · doi:10.1110/ps.041111405 · Cited by 102
Mutational analysis of domain antibodies reveals aggregation hotspots within and near the complementarity determining regions
Perchiacca, J. M., Bhattacharya, M., & Tessier, P. M. (2011) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.23085 · Cited by 101
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Adams, P. D., Baker, D. A., Brünger, A. T., Das, R., DiMaio, F., Read, R. J., Richardson, D. C., Richardson, J. S., & Terwilliger, T. C. (2013) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-083012-130253 · Cited by 101
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Braithwaite, E. R. (1964) · Elsevier eBooks · doi:10.1016/b978-0-08-010018-0.50006-1 · Cited by 100
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Lee, C. C., Perchiacca, J. M., & Tessier, P. M. (2013) · Trends in biotechnology · doi:10.1016/j.tibtech.2013.07.002 · Cited by 99
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Arosio, P., Rima, S., Lattuada, M., & Morbidelli, M. (2012) · The Journal of Physical Chemistry B · doi:10.1021/jp301091n · Cited by 95
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Arosio, P., Jaquet, B., Wu, H., & Morbidelli, M. (2012) · Biophysical Chemistry · doi:10.1016/j.bpc.2012.05.004 · Cited by 94
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Rowley, M. J., O’Connor, K., & Wijeyewickrema, L. C. (2004) · Biotechnology annual review · doi:10.1016/s1387-2656(04)10006-9 · Cited by 89
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Gámez, A., Pérez, B., Ugarte, M., & Desviat, L. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003231200 · Cited by 86
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Papanikolopoulou, K., Mills-Henry, I., Thol, S., Wang, Y., Gross, A. A. R., Kirschner, D. A., Decatur, S. M., & King, J. (2008) · PubMed Central · Cited by 75
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Shi, Y., Rhodes, N. R., Abdolvahabi, A., Kohn, T. P., Cook, N. P., Martı́, A. A., & Shaw, B. F. (2013) · Journal of the American Chemical Society · doi:10.1021/ja407801x · Cited by 74
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Banks, D. D., Latypov, R. F., Ketchem, R. R., Woodard, J., Scavezze, J. L., Siska, C. C., & Razinkov, V. I. (2012) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23219 · Cited by 69
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Jha, R. K., Leaver‐Fay, A., Yin, S., Wu, Y., Butterfoss, G. L., Szyperski, T., Dokholyan, N. V., & Kuhlman, B. A. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.05.006 · Cited by 68
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Authors: Roberts, C. J.
Affiliations: University of Delaware (US)
Corresponding author: Roberts, Christopher J.
ORCID: Roberts, Christopher J.
Venue: Trends in Biotechnology
Publisher: Elsevier BV
Published: 2014-07
Volume: 32
Issue: 7
Pages: 372-380
ISSN: 0167-7799 (ISSN-L)
DOI: 10.1016/j.tibtech.2014.05.005
PMC: PMC4146573
OpenAlex: W1972260684
Cited by: 455
References: 102
Citations by year: 2026: 46 · 2025: 35 · 2024: 39 · 2023: 41 · 2022: 38 · 2021: 48 · 2020: 53 · 2019: 58 · 2018: 46 · 2017: 26 · 2016: 16 · 2015: 7 · 2014: 2
FWCI: 1.60
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in biotechnology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Science Foundation
Foundation for the National Institutes of Health
National Institute of Biomedical Imaging and Bioengineering (R01EB006006)
National Center for Research Resources (P20RR015588)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords: protein stability, aggregation-prone proteins, partially unfolded state, aggregation control, protein design, protein environment
MeSH terms: Biopharmaceutics, Biotechnology, Humans, Models, Molecular, Protein Conformation, Proteins, Protein Folding, Protein Stability, Protein Aggregates

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Therapeutic protein aggregation: mechanisms, design, and control

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