The blood-brain barrier (BBB) represents one of the greatest obstacles in developing medicines for brain disorders. This selective interface protects the central nervous system while limiting therapeutic compound entry. Brain microvascular endothelial cells with tight junctions, supported by astrocytes, pericytes and specialized extracellular matrix, form the BBB. It restricts most drugs, with over 98 percent of small molecules and virtually all biologics failing to reach brain targets. This is especially relevant for oncology, neurodegenerative, metabolic and neuroinflammation research.
Developing successful BBB-crossing therapies requires a multifaceted approach. To advance their CNS candidates, teams must access broad antibody diversity and highly predictive models, execute rigorous permeability and species cross-reactivity assays, and generate robust developability data. Cyagen’s BBB platform covers the full process for drug discovery and CNS delivery validation. We handle the heavy lifting, from immunization and affinity maturation to the validation of BBB-shuttle antibodies and nanobody delivery systems. Whether you are working with biologics or AAV vectors, our in vivo models for receptor-mediated transcytosis (RMT), including TfR1-mediated pathways and other targets, provide the definitive data needed to progress your CNS program.
Bypass the complexities of central nervous system (CNS) targeting with Cyagen's established portfolio of discovery-ready BBB shuttle antibodies. Developed through our comprehensive HUGO-Ab™ antibody discovery platform, these assets have been successfully generated and validated using our specialized, regionally humanized mouse strains. By targeting validated transport pathways like TFR1, CD98HC and IGF1R, our antibodies facilitate efficient receptor-mediated transcytosis (RMT) to deliver therapeutic payloads across the blood-brain barrier.
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Physiologically Relevant Receptor-Mediated Assays
The development of effective therapies for Alzheimer's disease (AD) is frequently hindered by the blood-brain barrier (BBB), which restricts the delivery of potential therapeutic agents to the central nervous system. To overcome this limitation, researchers are increasingly focused on developing BBB-shuttle technologies that leverage receptor-mediated transcytosis to ferry biologics and AAV vectors into the brain.
Achieving success in these programs requires high-quality, biologically relevant models. Cyagen differentiated both APPSwe/Swe and control iPSCs into mature cortical neurons, creating a robust platform for testing BBB delivery strategies. Comprehensive marker and electrophysiological data confirm clear neuronal identity and functional maturation, providing a precise system to evaluate transport receptor performance and its impact on neuronal health in an AD context.
Advance your blood-brain barrier (BBB) targeted drug screening and discovery programs with Cyagen’s extensive portfolio of humanized mouse models. Our comprehensive collection features a wide array of single, double, and triple humanized strains that target key transport receptors such as huTFRC（humanized TfR1 mouse model） and huCD98HC. These models are often crossed with relevant disease backgrounds - such as huTau, huSNCA, huDMD - offering translational neurodegenerative disease mouse models and rare disease backgrounds. Fully validated for in vivo applications, these strains deliver a highly predictive and reliable platform to evaluate receptor-mediated transcytosis (RMT), assess brain penetration, and determine therapeutic efficacy for next-generation CNS therapies.
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Beyond model generation, Cyagen serves as your integrated preclinical partner. We offer a specialized suite of downstream analytical services tailored for blood-brain barrier permeability testing and CNS pharmacodynamics.
Whether you are evaluating the transcytosis of an AAV vector delivered via intravenous injection or quantifying the brain concentration of a bispecific antibody, our functional validation pipeline is designed to generate robust, IND-enabling data. We comprehensively elucidate the molecular mechanisms, safety profile, and on-target delivery efficacy of your therapeutic candidates.
| Analysis Category | Key Applications in BBB & CNS Research | Specific Services |
|---|---|---|
| Gene & Protein Expression | Validation of human receptor expression and absence of mouse ortholog in humanized models; supports research on receptor function in iron metabolism, amino acid transport, cancer, and neurodegenerative diseases | RT-qPCR to quantify human vs. mouse gene transcripts in multiple tissues (brain regions, liver, kidney, spinal cord) |
| Western Blot for protein expression in brain and peripheral tissues | ||
| Flow Cytometry for surface protein expression on relevant cell populations | ||
| Histology & IHC/IF | Visualization of human receptor localization in cerebral microvascular endothelium; key for BBB drug delivery studies | Co-immunostaining of human receptor protein with endothelial cell marker in brain tissue sections |
| Pharmacodynamic & Functional Validation | Preclinical evaluation of human receptor-dependent antibody transport across the blood-brain barrier and confirmation of BBB integrity | In vivo assessment of receptor-mediated CNS delivery using bispecific antibody (brain cortex vs. serum concentrations) |
| 2% Evans Blue assay to evaluate BBB permeability/integrity | ||
| Hematological & Phenotypic Analysis | Phenotypic characterization including effects on hematology, iron homeostasis, and immune cell distribution for disease modeling and therapeutic safety assessment | Complete Blood Count (CBC) including erythrocyte parameters, hemoglobin, platelets |
| Serum iron level quantification | ||
| Flow cytometric profiling of major immune cell subsets in bone marrow, blood, and spleen |
