ArticlemAbs
Potential aggregation prone regions in biotherapeutics: A survey of commercial monoclonal antibodies.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed.
- Understanding the Aggregation Mechanism of and Developing Stabilization Strategies for Recombinant Fibroblast Growth Factor 2.Biomolecules · 2026Article
- Engineering mammalian protein secretion: Toward the convergence of high-throughput biology and computational methods.Cell systems · 2025Review
- PROPERMAB: an integrative framework formAbs · 2025Article
- Investigating Local Sequence-Structural Attributes of Amyloidogenic Light Chain Variable Domains.Proteins · 2025Article
- Highly variable aggregation and glycosylation profiles and their roles in immunogenicity to protein-based therapeutics.Journal of pharmaceutical sciences · 2025Review
- Antibody Aggregation: A Problem Within the Biopharmaceutical Industry and Its Role in AL Amyloidosis Disease.The protein journal · 2025Review
- Revolutionizing Synthetic Antibody Design: Harnessing Artificial Intelligence and Deep Sequencing Big Data for Unprecedented Advances.Molecular biotechnology · 2025Review
- Advanced computational approaches to understand protein aggregation.Biophysics reviews · 2024Review
- Site-Specific Structural Changes in Long-Term-Stressed Monoclonal Antibody Revealed with DEPC Covalent-Labeling and Quantitative Mass Spectrometry.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Single-chain dimers from de novo immunoglobulins as robust scaffolds for multiple binding loops.Nature communications · 2023Article
- Efficiency Comparative Approach of Plant-Produced Monoclonal Antibodies against Rabies Virus Infection.Vaccines · 2023Article
- Comparison of hydrophobicity scales for predicting biophysical properties of antibodies.Frontiers in molecular biosciences · 2022Article
- Antibody interfaces revealed through structural mining.Computational and structural biotechnology journal · 2022Article
- Expanding the toolbox for predictive parameters describing antibody stability considering thermodynamic and kinetic determinants.Pharmaceutical research · 2021Article
- Exploring the sequence features determining amyloidosis in human antibody light chains.Scientific reports · 2021Article
- Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- Protein aggregation: in silico algorithms and applications.Biophysical reviews · 2021Review
- Generation and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody.Scientific reports · 2021Article
- Micro-Heterogeneity of Antibody Molecules.Experientia supplementum (2012) · 2021Review
- Functions of Gle1 are governed by two distinct modes of self-association.The Journal of biological chemistry · 2020Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aggregation of a biotherapeutic is of significant concern and judicious process and formulation development is required to minimize aggregate levels in the final product. Aggregation of a protein in solution is driven by intrinsic and extrinsic factors. In this work we have focused on aggregation as an intrinsic property of the molecule. We have studied the sequences and Fab structures of commercial and non-commercial antibody sequences for their vulnerability towards aggregation by using sequence based computational tools to identify potential aggregation-prone motifs or regions. The mAbs in our dataset contain 2 to 8 aggregation-prone motifs per heavy and light chain pair. Some of these motifs are located in variable domains, primarily in CDRs. Most aggregation-prone motifs are rich in beta branched aliphatic and aromatic residues. Hydroxyl-containing Ser/Thr residues are also found in several aggregation-prone motifs while charged residues are rare. The motifs found in light chain CDR3 are glutamine (Q)/asparagine (N) rich. These motifs are similar to the reported aggregation promoting regions found in prion and amyloidogenic proteins that are also rich in Q/N, aliphatic and aromatic residues. The implication is that one possible mechanism for aggregation of mAbs may be through formation of cross-beta structures and fibrils. Mapping on the available Fab-receptor/antigen complex structures reveals that these motifs in CDRs might also contribute significantly towards receptor/antigen binding. Our analysis identifies the opportunity and tools for simultaneous optimization of the therapeutic protein sequence for potency and specificity while reducing vulnerability towards aggregation.
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