Featured
-
-
Article
| Open AccessThe Fab region of IgG impairs the internalization pathway of FcRn upon Fc engagement
Disrupting the association between the Immunoglobulin G constant fragment (Fc) and the neonatal Fc receptor (FcRn) by engineered antibodies is a promising strategy to reduce autoantibody levels in autoimmune diseases. Here authors show that the variable fragment (Fab) of immunoglobulins could disturb the Fc-FcRn interaction, therefore the therapeutic effect of Fc-only fragments might surpass that of Fc-engineered antibodies with enhanced binding to FcRn.
- Maximilian Brinkhaus
- , Erwin Pannecoucke
- & Gestur Vidarsson
-
Article
| Open AccessA 33-residue peptide tag increases solubility and stability of Escherichia coli produced single-chain antibody fragments
Low solubility and stability of Escherichia coli produced single chain variable fragments (scFvs) restrict their applications. Here the authors report a 33-residue peptide tag which simultaneously increases the solubility and thermostability of multiple scFvs produced in Escherichia coli SHuffle strain.
- Yang Wang
- , Wenjie Yuan
- & Yong-Xiang Wang
-
Article
| Open AccessBlocking phospholamban with VHH intrabodies enhances contractility and relaxation in heart failure
Here the authors use modified RNA and VHH libraries to generate intrabodies that target dysregulated interactions between two calcium handling proteins in failing cardiomyocytes. Heart specific expression of the intrabodies in a murine heart failure model results in improved cardiac function.
- Erwin De Genst
- , Kylie S. Foo
- & Kenneth R. Chien
-
Article
| Open AccessMechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography
Shark antibodies (Variable New Antigen Receptors, VNARs) are the smallest naturally occurring antibody fragments. Here, the authors screen a VNAR phage display library against the SARS-CoV2 receptor binding domain (RBD) and identify VNARs that neutralize the SARSCoV-2 virus and discuss their mechanisms of viral neutralization.
- Obinna C. Ubah
- , Eric W. Lake
- & Caroline J. Barelle
-
Article
| Open AccessA potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19
Neutralizing nanobodies (Nb) are of considerable interest as therapeutic agents for COVID-19 treatment. Here, the authors functionally and structurally characterize Nbs that bind with high affinity to the receptor binding domain of the SARS-CoV-2 spike protein and show that an engineered homotrimeric Nb prevents disease progression in a Syrian hamster model of COVID-19 when administered intranasally.
- Jiandong Huo
- , Halina Mikolajek
- & Raymond J. Owens
-
Article
| Open AccessA cell-free nanobody engineering platform rapidly generates SARS-CoV-2 neutralizing nanobodies
Faster, higher throughput antibody engineering methods are needed. Here the authors present CeVICA, a cell-free nanobody engineering platform using ribosome display and computational clustering analysis for in vitro selection; they use this to develop nanobodies against the RBD of SARS-CoV-2 spike protein.
- Xun Chen
- , Matteo Gentili
- & Aviv Regev
-
Article
| Open AccessSelective targeting of ligand-dependent and -independent signaling by GPCR conformation-specific anti-US28 intrabodies
Various GPCRs display constitutive ligand-independent activity, but it remains unclear whether ligand-dependent and -independent conformations differ. Here the authors demonstrate the recognition and blocking of G protein recruitment of either the ligand-bound active, or the constitutively active apo-conformation of the viral GPCR US28 by different nanobodies that target similar intracellular loops of the receptor.
- Timo W. M. De Groof
- , Nick D. Bergkamp
- & Martine J. Smit
-
Article
| Open AccessDutaFabs are engineered therapeutic Fab fragments that can bind two targets simultaneously
Bispecific antibodies can bind to two distinct targets though the fusion of two different Fv regions. In this study, the authors develop DutaFabs that present two separated and independent antigen binding sites within the same Fv region, giving rise to bispecific Fab fragments.
- Roland Beckmann
- , Kristian Jensen
- & Hubert Kettenberger
-
Article
| Open AccessHumanized single domain antibodies neutralize SARS-CoV-2 by targeting the spike receptor binding domain
Here, using a humanized phage display library with recombinant SARS- CoV-2 receptor binding domain (RBD) proteins, the authors identify a number of single domain antibodies (sdAbs) that neutralize SARS-CoV-2 in vitro by inhibiting the interaction of the RDB with the host entry receptor ACE2.
- Xiaojing Chi
- , Xiuying Liu
- & Wei Yang
-
Article
| Open AccessOsteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation
Osteoarthritis (OA) is associated with cartilage disruption, but the underlying mechanisms remain unclear. Here, the authors show that expression of osteoclast-associated receptor (OSCAR) is associated with OA, that its genetic ablation or targeting with OSCAR-Fc fusion protein ameliorates OA in mice by decreasing chondrocyte apoptosis.
- Doo Ri Park
- , Jihee Kim
- & Soo Young Lee
-
Article
| Open AccessSelective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains
STAT3 is an attractive therapeutic target but its homology with other STAT proteins complicates the development of selective inhibitors. Here, the authors develop monobodies with high affinity and selectivity for STAT3 and show that they can interfere with cellular STAT3 activity.
- Grégory La Sala
- , Camille Michiels
- & Oliver Hantschel
-
Article
| Open AccessAnti-LRP5/6 VHHs promote differentiation of Wnt-hypersensitive intestinal stem cells
Enhanced Wnt receptor activity is a major cause of cancer development. Here the authors identify camelid single-domain antibody fragments (VHHs) that bind to the Wnt receptor LRP5/6 ectodomain, determine the crystal structures and show that these VHHs selectively inhibit Wnt3- mediated cellular responses and block the growth of mutant Wnt-hypersensitive intestinal tumor organoids.
- Nicola Fenderico
- , Revina C. van Scherpenzeel
- & Madelon M. Maurice
-
Article
| Open AccessOxidation-specific epitopes restrain bone formation
Atherosclerosis and osteoporosis are epidemiologically associated, and oxidation specific epitopes (OSEs), which can be neutralized by innate antibodies, are pathogenic for both. Here, the authors show that mice expressing antibody fragments targeted to OSEs are protected from the bone loss induced by high-fat diet and have increased bone mass when fed a normal diet, and that levels of innate antibodies to OSEs decrease with ageing.
- Elena Ambrogini
- , Xuchu Que
- & Robert L. Jilka
-
Article
| Open AccessGenetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin
The therapeutic use of single-chain antibodies (VHHs) is limited by their short half-life in the circulation. Here the authors engineer mouse and human red blood cells to express VHHs against botulinum neurotoxin A (BoNT/A) on their surface and show that an infusion of these cells into mice confers long lasting protection against a high dose of BoNT/A.
- Nai-Jia Huang
- , Novalia Pishesha
- & Harvey F. Lodish
-
Article
| Open AccessLong-acting protein drugs for the treatment of ocular diseases
Retinal vascular disease treatments involve frequent pharmacological intraocular administrations. Here the authors present a method to increase the half-life of injected drugs by fusing these to a hyaluronan-binding peptide, which might lead to less frequent retinal disease treatments.
- Joy G. Ghosh
- , Andrew A. Nguyen
- & Michael Roguska
-
Article
| Open AccessPotent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state
Neutralizing antibodies for respiratory syncytial virus (RSV) can reduce disease in hospitalized children, but current options show limited efficacy. Here, the authors isolate potent single-domain antibodies from llamas that recognize the prefusion conformation of RSV F and prevent RSV replication in mice.
- Iebe Rossey
- , Morgan S. A. Gilman
- & Xavier Saelens