Aggregation is a common problem affecting biopharmaceutical development that can have a significant effect on the quality of the product, as well as the safety to patients, particularly because of the increased risk of immune reactions. Here, we describe a new high-throughput screening algorithm developed to classify antibody molecules based on their propensity to aggregate. The tool, constructed and validated on experimental aggregation data for over 500 antibodies, is able to discern molecules with a high aggregation propensity as defined by experimental criteria relevant to bioprocessing and manufacturing of these molecules. Furthermore, we show how this tool can be combined with other computational approaches during early drug development to select molecules with reduced risk of aggregation and optimal developability properties.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622581 | PMC |
| http://dx.doi.org/10.1080/19420862.2015.1007828 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Serine phosphorylation facilitates protein degradation by the human mitochondrial ClpXP protease.
Proc Natl Acad Sci U S A
February 2025
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada.
ClpXP is a two-component mitochondrial matrix protease. The caseinolytic mitochondrial matrix peptidase chaperone subunit X (ClpX) recognizes and translocates protein substrates into the degradation chamber of the caseinolytic protease P (ClpP) for proteolysis. ClpXP degrades damaged respiratory chain proteins and is necessary for cancer cell survival.
View Article and Find Full Text PDFHsp90, DnaK, and ClpB collaborate in protein reactivation.
Proc Natl Acad Sci U S A
February 2025
Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892.
Hsp70, Hsp90, and ClpB/Hsp100 are molecular chaperones that help regulate proteostasis. Bacterial and yeast Hsp70s and their cochaperones function synergistically with Hsp90s to reactivate inactive and aggregated proteins by a mechanism that requires a direct interaction between Hsp90 and Hsp70 both in vitro and in vivo. and yeast Hsp70s also collaborate in bichaperone systems with ClpB and Hsp104, respectively, to disaggregate and reactivate aggregated proteins and amyloids such as prions.
View Article and Find Full Text PDFThe ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity.
PLoS Biol
January 2025
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Ubiquitin-conjugating enzymes (E2s) are key for protein turnover and quality control via ubiquitination. Some E2s also physically interact with the proteasome, but it remains undetermined which E2s maintain proteostasis during aging. Here, we find that E2s have diverse roles in handling a model aggregation-prone protein (huntingtin-polyQ) in the Drosophila retina: while some E2s mediate aggregate assembly, UBE2D/effete (eff) and other E2s are required for huntingtin-polyQ degradation.
View Article and Find Full Text PDFFamilial Steep Corneas in Posterior Polymorphous Corneal Dystrophy 3 Due to a Novel ZEB1 Gene Mutation.
Cornea
January 2025
Department of Ophthalmology, Edith Wolfson Medical Center, Holon, Israel.
Purpose: To present 4 family members with posterior polymorphous corneal dystrophy (PPCD), nonkeratoconic steep corneas, and myopia caused by a previously unknown genetic alteration in the ZEB1 gene.
Methods: Ophthalmic examinations and corneal curvature analyses were performed for all patients. Whole-exome targeted gene panel sequencing was performed for 1 patient.
Genomic Analysis Reveals Racial and Age-Related Differences in the Somatic Landscape of Breast Cancer and the Association with Socioeconomic Factors.
Cancer Res
January 2025
University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Cancer genomics consortia have identified somatic drivers of breast cancer subtypes. However, these studies have predominantly included older, non-Black women, and the related socioeconomic status (SES) data is limited. Increased representation and depth of social data are crucial for understanding how health inequity is intertwined with somatic landscapes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!