ArticlePloS one2015
Engineering an Anti-Transferrin Receptor ScFv for pH-Sensitive Binding Leads to Increased Intracellular Accumulation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
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- pH-Responsive Polyethylene Glycol Engagers for Enhanced Brain Delivery of PEGylated Nanomedicine to Treat Glioblastoma.ACS nano · 2025Article
- Comparative Performance of High-Throughput Methods for Protein pJournal of chemical information and modeling · 2023Article
- Enhanced in vivo blood brain barrier transcytosis of macromolecular cargo using an engineered pH-sensitive mouse transferrin receptor binding nanobody.Fluids and barriers of the CNS · 2023Article
- EnhancedbioRxiv : the preprint server for biology · 2023Article
- Identification of lamprey variable lymphocyte receptors that target the brain vasculature.Scientific reports · 2022Article
- Biology drives the discovery of bispecific antibodies as innovative therapeutics.Antibody therapeutics · 2020Review
- A yeast display immunoprecipitation screen for targeted discovery of antibodies against membrane protein complexes.Protein engineering, design & selection : PEDS · 2019Article
- Capture and display of antibodies secreted by hybridoma cells enables fluorescent on-cell screening.mAbs · 2019Article
- Engineering Allostery into Proteins.Advances in experimental medicine and biology · 2019Review
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- Strategies to identify, engineer, and validate antibodies targeting blood-brain barrier receptor-mediated transcytosis systems for CNS drug delivery.Expert opinion on drug deliveryReview
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The equilibrium binding affinity of receptor-ligand or antibody-antigen pairs may be modulated by protonation of histidine side-chains, and such pH-dependent mechanisms play important roles in biological systems, affecting molecular uptake and trafficking. Here, we aimed to manipulate cellular transport of single-chain antibodies (scFvs) against the transferrin receptor (TfR) by engineering pH-dependent antigen binding. An anti-TfR scFv was subjected to histidine saturation mutagenesis of a single CDR. By employing yeast surface display with a pH-dependent screening pressure, scFvs having markedly increased dissociation from TfR at pH 5.5 were identified. The pH-sensitivity generally resulted from a central cluster of histidine residues in CDRH1. When soluble, pH-sensitive, scFv clone M16 was dosed onto live cells, the internalized fraction was 2.6-fold greater than scFvs that lacked pH-sensitive binding and the increase was dependent on endosomal acidification. Differences in the intracellular distribution of M16 were also observed consistent with an intracellular decoupling of the scFv M16-TfR complex. Engineered pH-sensitive TfR binding could prove important for increasing the effectiveness of TfR-targeted antibodies seeking to exploit endocytosis or transcytosis for drug delivery purposes.
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Registered trials
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