당신도 좋아할 수 있습니다
Central nervous system (CNS) diseases such as Alzheimer’s, Parkinson’s, stroke, and brain tumors represent a growing global health burden. However, developing effective treatments remains a major challenge due to the blood-brain barrier (BBB), which blocks over 98% of small molecules and nearly all large molecules from reaching the brain (Wu et al. 2023).
In April 2025, two milestones spotlighted the accelerating race to overcome the BBB:
Denali Therapeutics filed a BLA for Tividenofusp Alfa, a BBB-penetrant therapy for Hunter Syndrome.
GSK entered a $2.75B licensing deal with ABL Bio for its Grabody-B BBB shuttle platform.
These moves signal a growing focus on receptor-mediated transcytosis (RMT)—a method of using receptors on brain capillaries to shuttle drugs into the CNS.
 |
TfR1 and CD98HC in Receptor-Mediated Brain Delivery Systems |
TfR1 & CD98HC: A Dual-Gate Strategy
Dual-targeting both TfR1 and CD98HC represents a next-generation strategy that may optimize brain penetration while mitigating systemic toxicity—offering a more balanced and effective solution for CNS drug delivery.
TfR1 (Transferrin Receptor 1): A well-established BBB transporter with strong uptake but high peripheral expression, which may cause rapid clearance and off-target effects like anemia (Candelaria et al. 2021).
CD98HC (CD98 Heavy Chain): A component of amino acid transporters with more selective expression and potential for sustained, brain-targeted delivery (Pornnoppadol et al. 2024).
Target Humanized Models to Advance BBB-Penetrant Therapeutics
Biocytogen offers single- and multi-target humanized animal models expressing key BBB transport receptors—TfR1, CD98HC, IGF1R, and LDLR family—to support preclinical testing of antibodies, AAVs, and AOCs. These models enable efficient evaluation of efficacy and safety for next-gen BBB-penetrant therapies.
Highlighted BBB Target Humanized Models:
Case study
In Vivo PK Evaluation of Anti-TFR1 and CD98HC Antibodies in TFR1/CD98HC Humanized Mice |
 |
B-hTFR1/hCD98HC mice were intravenously injected via the tail vein with one of the following: control IgG (10 mg/kg), anti-human TFR1 antibody (JR-141 analog, monovalent, in-house, 12.56 mg/kg), or anti-human CD98HC antibody (CD98BBBB-h1.L analog, monovalent, in-house, 13.3 mg/kg). Brain tissues were collected for in vivo PK analysis. Brain antibody concentrations (A) and % of injected dose per gram of brain tissues (B) were quantified. Mean ± SEM. |
Conclusion
|
Humanized Mouse Models for BBB Research at Biocytogen |
The Future of Brain Drug Delivery From receptor-mediated transport to innovative capsid design and humanized in vivo models, researchers now have more tools than ever to overcome the challenges of the blood-brain barrier. As the field evolves, Biocytogen’s BBB platform stands ready to support the development of smarter, more effective therapies for the brain. Contact us to learn how our models can accelerate your CNS discovery and development efforts! Reference: Wu, Di, et al. "The blood–brain barrier: Structure, regulation and drug delivery." Signal transduction and targeted therapy 8.1 (2023): 217. Edavettal, Suzanne, et al. "Enhanced delivery of antibodies across the blood-brain barrier via TEMs with inherent receptor-mediated phagocytosis." Med 3.12 (2022): 860-882. Candelaria, Pierre V., et al. "Antibodies targeting the transferrin receptor 1 (TfR1) as direct anti-cancer agents." Frontiers in immunology 12 (2021): 607692. Pornnoppadol, Ghasidit, et al. "Bispecific antibody shuttles targeting CD98hc mediate efficient and long-lived brain delivery of IgGs." Cell chemical biology 31.2 (2024): 361-372. |
