ArticleFluids and barriers of the CNS2020
Identification and in vivo characterization of a brain-penetrating nanobody.
Article in Fluids and barriers of the CNS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 81 citations in OpenAlex.
- Article
- High-Affinity Nanobody Against the LEDGF PWWP Domain Inhibits Chromatin Binding In Vitro.Biomolecules · 2026Article
- Engineering a dimeric single-domain antibody for improved detection and neutralization of amyloid-β oligomers.Communications biology · 2026Article
- Nanobody Therapeutics in Alzheimer's Disease: From Molecular Mechanisms to Translational Approaches.Antibodies (Basel, Switzerland) · 2025Review
- Article
- Beyond amyloid: nanobody-mediated neuroinflammatory therapy for Alzheimer's disease.Translational neurodegeneration · 2025Review
- Identification of Variable Lymphocyte Receptors That Target the Human Blood-Brain Barrier.Pharmaceutics · 2025Article
- Article
- Harnessing Nanobodies for Precision Targeting of Proteoforms: Opportunities and Challenges in Therapeutics and Diagnostics.ACS chemical biology · 2025Review
- Breaking Barriers: Delivering Therapeutics to the Brain in Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025Article
- Brain-penetrant complement inhibition mitigates neurodegeneration in an Alzheimer's disease mouse model.Brain : a journal of neurology · 2025Article
- Increasing brain half-life of antibodies by additional binding to myelin oligodendrocyte glycoprotein, a CNS specific protein.Fluids and barriers of the CNS · 2025Article
- Targeting Brain Drug Delivery with Macromolecules Through Receptor-Mediated Transcytosis.Pharmaceutics · 2025Review
- Nanoparticle targeting strategies for traumatic brain injury.Journal of neural engineering · 2024Review
- Discovery of nanobodies: a comprehensive review of their applications and potential over the past five years.Journal of nanobiotechnology · 2024Review
- Single-Domain Antibodies as Antibody-Drug Conjugates: From Promise to Practice-A Systematic Review.Cancers · 2024Review
- A Potent Sybody Selectively Inhibits α-Synuclein Amyloid Formation by Binding to the P1 Region.Journal of medicinal chemistry · 2024Article
- In vivo neutralization of coral snake venoms with an oligoclonal nanobody mixture in a murine challenge model.Nature communications · 2024Article
- A single-domain antibody for the detection of pathological Tau protein in the early stages of oligomerization.Journal of translational medicine · 2024Article
- Neurotensin and Neurotensin Receptors in Stress-related Disorders: Pathophysiology & Novel Drug Targets.Current neuropharmacology · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 3 countries.
Funding
Abstract
backgroundPreclinical models to determine blood to brain transport ability of therapeutics are often ambiguous. In this study a method is developed that relies on CNS target-engagement and is able to rank brain-penetrating capacities. This method led to the discovery of an anti-transferrin receptor nanobody that is able to deliver a biologically active peptide to the brain via receptor-mediated transcytosis.
methodsVarious nanobodies against the mouse transferrin receptor were fused to neurotensin and injected peripherally in mice. Neurotensin is a neuropeptide that causes hypothermia when present in the brain but is unable to reach the brain from the periphery. Continuous body temperature measurements were used as a readout for brain penetration of nanobody-neurotensin fusions after its peripheral administration. Full temperature curves were analyzed using two-way ANOVA with Dunnett multiple comparisons tests.
resultsOne anti-transferrin receptor nanobody coupled to neurotensin elicited a drop in body temperature following intravenous injection. Epitope binning indicated that this nanobody bound a distinct transferrin receptor epitope compared to the non-crossing nanobodies. This brain-penetrating nanobody was used to characterize the in vivo hypothermia model. The hypothermic effect caused by neurotensin is dose-dependent and could be used to directly compare peripheral administration routes and various nanobodies in terms of brain exposure.
conclusionThis method led to the discovery of an anti-transferrin receptor nanobody that can reach the brain via receptor-mediated transcytosis after peripheral administration. This method could be used to assess novel proteins for brain-penetrating capabilities using a target-engaging readout.
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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.