ArticleNature communications2020
An in vivo platform to select and evolve aggregation-resistant proteins.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed.
- The Role of Microemulsions in Enhancing the Stability of Biopharmaceuticals.Drug design, development and therapy · 2026Review
- Global Analysis of Aggregation Determinants in Small Protein Domains.bioRxiv : the preprint server for biology · 2025Article
- Employing deep mutational scanning in theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Integrating Biochemical and Computational Approaches Reveal Structural Insights in Trastuzumab scFv-Fc Antibody Engineering.Biomolecules · 2025Article
- The development of a canine single-chain phage antibody library to isolate recombinant antibodies for use in translational cancer research.Cell reports methods · 2025Article
- AggNet: Advancing protein aggregation analysis through deep learning and protein language model.Protein science : a publication of the Protein Society · 2025Article
- Rationalizing mAb Candidate Screening Using a Single Holistic Developability Parameter.Molecular pharmaceutics · 2025Article
- Enzymatically catalyzed molecular aggregation.Nature communications · 2024Article
- Aggrescan4D: A comprehensive tool for pH-dependent analysis and engineering of protein aggregation propensity.Protein science : a publication of the Protein Society · 2024Review
- Sequence-developability mapping of affibody and fibronectin paratopes via library-scale variant characterization.Protein engineering, design & selection : PEDS · 2024Article
- Biophysical Analysis of Therapeutic Antibodies in the Early Development Pipeline.Biologics : targets & therapy · 2024Review
- Automated optimisation of solubility and conformational stability of antibodies and proteins.Nature communications · 2023Article
- Non-specificity as the sticky problem in therapeutic antibody development.Nature reviews. Chemistry · 2022Review
- Increasing protein stability by inferring substitution effects from high-throughput experiments.Cell reports methods · 2022Article
- Supramolecular Loading of DNA Hydrogels with Dye-Drug Conjugates for Real-Time Photoacoustic Monitoring of Chemotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Single residue modulators of amyloid formation in the N-terminal P1-region of α-synuclein.Nature communications · 2022Article
- The effect of mutation on an aggregation-prone protein: An in vivo, in vitro, and in silico analysis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Aggregation Time Machine: A Platform for the Prediction and Optimization of Long-Term Antibody Stability Using Short-Term Kinetic Analysis.Journal of medicinal chemistry · 2022Article
- High-throughput developability assays enable library-scale identification of producible protein scaffold variants.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- An enzyme-based biosensor for monitoring and engineering protein stability in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Protein biopharmaceuticals are highly successful, but their utility is compromised by their propensity to aggregate during manufacture and storage. As aggregation can be triggered by non-native states, whose population is not necessarily related to thermodynamic stability, prediction of poorly-behaving biologics is difficult, and searching for sequences with desired properties is labour-intensive and time-consuming. Here we show that an assay in the periplasm of E. coli linking aggregation directly to antibiotic resistance acts as a sensor for the innate (un-accelerated) aggregation of antibody fragments. Using this assay as a directed evolution screen, we demonstrate the generation of aggregation resistant scFv sequences when reformatted as IgGs. This powerful tool can thus screen and evolve 'manufacturable' biopharmaceuticals early in industrial development. By comparing the mutational profiles of three different immunoglobulin scaffolds, we show the applicability of this method to investigate protein aggregation mechanisms important to both industrial manufacture and amyloid disease.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.