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All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

In Vitro Evaluation of RMT-Targeting Biologics

Inquiry

As the demand for biologics targeting central nervous system (CNS) diseases continues to rise, overcoming the challenges of the blood-brain barrier (BBB) remains a critical hurdle in drug development. To ensure that CNS drugs reach their target sites with optimal efficacy, receptor-mediated transcytosis (RMT) has emerged as a promising strategy to facilitate the crossing of the BBB. Several in vitro BBB models have been developed to facilitate early screening and optimization of RMT-targeting biologics. In vitro evaluation of RMT-targeting biologics plays a pivotal role in optimizing and predicting the success of CNS drug delivery. These evaluations help identify effective strategies for enhancing brain penetration and provide valuable insights into the brain drug delivery system development process.

Internalization and transcytosis of OX26 antibody affinity variants in rat model of the BBB in vitro. — Fig. 1 Internalization and transcytosis of OX26 antibody affinity variants in rat model of the BBB *in vitro*. (Haqqani, *et al*., 2018)

Our Services

At Ace Therapeutics, our in vitro evaluation platform offers a suite of scientifically validated assays designed to assess the BBB transcytosis potential, intracellular trafficking efficiency within the endosomal compartment, and functional efficacy of RMT-targeting biologics. Our rigorous in vitro testing yields critical insights into the transcytosis efficiency and therapeutic potential of RMT-targeting biologics, ensuring they are well-optimized for downstream development.

Available In Vitro BBB Models

Mono cell cultures: Brain capillary endothelial cells (BCECs) from rat, mouse, porcine, bovine, or human origin; immortalized cells, such as the human cerebral microvascular endothelial cell line hCMEC/D3; human induced pluripotent stem cell (iPSC)-derived BBB models.
Co-cultures: BCECs and astrocytes/pericytes from rat, mouse, porcine, bovine, or human origin.
Triple cultures: BCECs co-cultured with a combination of two different cell types, such as astrocytes, pericytes, or neurons.
Microfluidic design model: A polycarbonate porous membrane with two channels that allow fluid to flow. Coculturing BCECs and astrocytes.

Our In Vitro Evaluation Services

Services	Description
RMT Receptor Binding Assays	These assays are designed to confirm that drug candidates specifically bind to and are internalized via their target RMT receptors, including the transferrin receptor, insulin receptor, and IGF1R. Surface Plasmon Resonance (SPR): Quantifies binding affinity between the drug candidate and the RMT receptor. Flow cytometry: Measures binding on the surface of live cells, with or without competition, to assess RMT receptor specificity and binding efficiency. Immunofluorescence microscopy: Tracks the internalization dynamics and subcellular localization of RMT-targeting biologics using labeled antibodies or fusion proteins.
In Vitro Transcytosis Assays	These assays allow us to help clients evaluate the ability of RMT-targeting biologics to undergo transcytosis in in vitro BBB models. Transwell-Based Assays: Utilize monoculture (e.g., hCMEC/D3, iPSC-derived endothelial cells) or co-culture models with astrocytes and pericytes. RMT-targeting biologics are added to the apical chamber, and samples are collected from the basolateral chamber at various time points. BBB disruption assay using TEER measurement, FITC-dextran and sodium fluorescein, Evans blue dye, etc. The concentration of RMT-targeting biologics in samples is determined by LC-MS/MS or ELISA. Permeability coefficients (Papp) and transcytosis efficiency are calculated.
Functional Efficacy Assays	These assays allow us to help clients assess whether the RMT-targeting biologics retain activity after transport across the BBB. Receptor activation assays: Confirm the functional engagement of the RMT-targeting biologic with its CNS target after transcytosis. Downstream bioactivity assays: Measure cell-based functional effects (e.g., neuroprotection, proliferation inhibition) of RMT-targeting biologics.

Advantages of Our Services

Featured In Vitro BBB Models

We provide a robust platform for screening RMT-targeting biologics by utilizing species-specific, high-performance in vitro BBB models. These models closely mimic human BBB conditions, allowing us to more reliably evaluate the ability of vector-payload candidates to reach the brain.

Dual-Use Platform for RMT-Targeting Ligands and Delivery Systems

Whether you are assessing a standalone therapeutic ligand or a cargo-carrying delivery platform, we offer customized assay designs:

For RMT-targeting ligands, we can confirm the BBB penetration and pharmacological activity of RMT-targeting biologics.
For delivery systems, we can evaluate the effect of vector on the transport and biological efficacy of RMT-targeting biologics post-transcytosis.

Time and Cost Efficiency

Our in vitro evaluation services streamline the development process by providing early-stage insights into the success potential of RMT-targeting biologics. This helps reduce costly late-stage failures, saving both time and resources in drug development.

At Ace Therapeutics, our mission is to advance the development of RMT-based brain drug delivery systems by providing rigorous in vitro evaluation services. Our expertise in receptor-mediated transcytosis and BBB models enables us to help you identify promising RMT-targeting biologics. Contact us today to learn more about our RMT-based brain drug delivery services.

Reference

Haqqani, A. S., et al. (2018). Intracellular sorting and transcytosis of the rat transferrin receptor antibody OX26 across the blood-brain barrier in vitro is dependent on its binding affinity. Journal of neurochemistry, 146(6), 735-752.