cDNA phage display is frequently used in drug development to screen for cellular target of drugs. However, in toxicology, cDNA phage display remains unexplored, although it has large potential in this field. In this study, cDNA phage display is demonstrated as a novel tool to screen for interactions between chemical compounds and cellular targets. The knowledge of these target interactions is valuable to have a more complete understanding of the mechanisms of action of chemical compounds. Bisphenol A (BPA) was selected as a model compound for this study. By selection of the cellular proteins that bind BPA with cDNA phage display, it was possible to identify a known cellular target of BPA, tubulin alpha and a possible novel cellular target of BPA, transforming acidic coiled-coil containing protein 3. Both these cellular proteins are involved in the mechanism of cell division. The disruption of cell division is a known non-genomic effect of BPA. Non-genomic effects are not mediated by differences in gene expression and therefore important mechanistic information might be missed with the widely used differential gene expression techniques for mode of action research. This cDNA phage display technique can provide important additional information about the interaction of chemical compounds with cellular targets that mediates these non-genomic actions and therefore gives complementary information to toxicogenomic studies to obtain a more complete understanding of the mechanism of action of chemical compounds.
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http://dx.doi.org/10.1016/j.tiv.2010.04.003 | DOI Listing |
Cancer continues to represent a substantial burden in terms of its morbidity and mortality, underscoring the imperative for the development of novel and efficacious treatment modalities. Recent advances in cancer immunotherapy have highlighted the importance of identifying tumour-specific antigens, which can assist the immune system in targeting malignant cells effectively. Phage display technology has emerged as an effective tool for the discovery of novel antigens through cDNA library screening, representing a significant advancement in the field of immunological research.
View Article and Find Full Text PDFNat Rev Drug Discov
December 2024
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, USA.
Clustered regularly interspaced short palindromic repeats (CRISPR) technology has transformed molecular biology and the future of gene-targeted therapeutics. CRISPR systems comprise a CRISPR-associated (Cas) endonuclease and a guide RNA (gRNA) that can be programmed to guide sequence-specific binding, cleavage, or modification of complementary DNA or RNA. However, the application of CRISPR-based therapeutics is challenged by factors such as molecular size, prokaryotic or phage origins, and an essential gRNA cofactor requirement, which impact efficacy, delivery and safety.
View Article and Find Full Text PDFBiotechnol Appl Biochem
December 2024
Institute of Physical Science and Information Technology, Anhui University, Hefei, Anhui, China.
In this study, we aimed to develop nanobodies targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1) for cancer diagnosis and therapy. We immunized alpacas with ROR1, extracted RNA from their blood, and converted it to complementary DNA (cDNA) to amplify the VHH (variable domain of heavy-chain antibodies) sequence. This sequence was used to construct a phage library with a capacity of 8 ×10.
View Article and Find Full Text PDFRMD Open
November 2024
Department of Immunology and Infection, Biomedical Research Institute, UHasselt, Hasselt, Belgium
Objective: To discover antibody biomarkers that can predict a lack of response to first-line therapy in rheumatoid arthritis (RA) patients.
Methods: Two RA cDNA phage display libraries were screened for novel antibodies in baseline RA sera from the Care in early RA (CareRA) trial, differentiating between patients who did or did not reach remission after first-line therapy (n=20 each). Antibody reactivity to identified University Hasselt (UH)-RA antigens was validated in baseline samples from 136 additional CareRA participants.
Soft Matter
October 2024
Department of Bionanoscience, TU Delft, 2629 HZ Delft, The Netherlands.
Weak multivalent interactions govern a large variety of biological processes like cell-cell adhesion and virus-host interactions. These systems distinguish sharply between surfaces based on receptor density, known as superselectivity. Present experimental studies typically involve tens or hundreds of interactions, resulting in a high entropic contribution leading to high selectivities.
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