The DOI matches its Crossref record; 101 of the 102 references it cites were found in a registry or an index.
Therapeutic protein aggregation: mechanisms, design, and control
Open accessAbstract
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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“Aggregates of capsids, as the third potential CQA, represent another product-related impurity with detrimental impact on safety and long-term stability of the vector product, as even trace amounts (e.g., <1%) provide nucleation sites for further aggregation.28,44,45”
From Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies (2021) · cites this paper as [45]
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Cites
Intermolecular and Surface Forces
(2011) · Elsevier eBooks · doi:10.1016/b978-0-12-391927-4.10024-6 · Cited by 17,242
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
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Wang, Y., Jiang, X., Feng, F., Liu, W., & Sun, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.08.001 · Cited by 335
Protein aggregation and its impact on product quality
Roberts, C. J. (2014) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2014.08.001 · Cited by 318
Self-citationConsiderations for the Design of Antibody-Based Therapeutics
Goulet, D. R., & Atkins, W. M. (2019) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2019.05.031 · Cited by 328
Protein aggregation – Mechanisms, detection, and control
Wang, W., & Roberts, C. J. (2018) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2018.08.043 · Cited by 328
Self-citationProtein aggregation, particle formation, characterization & rheology
Amin, S., Barnett, G. V., Pathak, J. A., Roberts, C. J., & Sarangapani, P. S. (2014) · Current Opinion in Colloid & Interface Science · doi:10.1016/j.cocis.2014.10.002 · Cited by 283
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Metadata
- Authors
- Roberts, C. J.
- Affiliations
- University of Delaware (US)
- Corresponding author
- 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)
- 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
- 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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