BBBporter™ Technology Platform

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Project Description

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

RMT-Targeting Vector Optimization and Validation Services

Inquiry

Receptor-mediated transcytosis (RMT) has emerged as a promising strategy for non-invasive, targeted delivery of drugs across the blood-brain barrier (BBB). However, the success of RMT-based brain drug delivery platforms depends not only on RMT receptor selection but also on optimizing and validating the RMT-targeting vectors. Although RMT-targeting vectors with enhanced tissue specificity can improve the efficiency of brain drug delivery, the intrinsic limitations of transcellular transport in each RMT system may impact overall success. Therefore, a deeper understanding of the properties of RMT-targeting vectors, such as antibody affinity and avidity, pH sensitivity of the antibody-antigen interaction, can facilitate the development of more effective BBB drug delivery vectors.

Engineered constructs and binding affinities of various anti-TfR antibodies designed to enhance transcytosis across the BBB. — Fig. 1 Constructs and binding affinity of the various anti-TfR antibodies engineered to improve BBB transcytosis. (Lajoie, *et al*., 2015)

Our Services

At Ace Therapeutics, we specialize in optimizing and validating RMT-targeting vectors, helping biotech and pharmaceutical companies improve the brain penetration of their therapeutics. Our platform focuses on optimizing the properties of RMT-targeting vectors, and validating their intracellular trafficking and BBB transcytosis in vitro and in vivo.

RMT-Targeting Vector Optimization Services

RMT-Targeting Antibody Optimization

We help our clients develop antibodies that target different RMT receptors. We use antibody engineering techniques to optimize these RMT-targeting vectors, generating variants with unique properties that can be tailored to specific applications.

Methods	Services
Affinity Tuning	Fine-tuning the binding affinity of antibodies to RMT receptors (e.g., TfR, CD98hc, Basigin, IR, and IGF1R) by engineering their variable regions.
Avidity and Valency Engineering	Designing monovalent or bivalent formats for different RMT-targeting antibodies to enhance brain uptake effects.
pH-Sensitive Antibody Design	Tuning the pH sensitivity of the RMT-targeting antibodies via histidine mutagenesis in the antibody binding regions to enhance their transcytosis ability.
Fc Region Optimization	Reducing off-target effects related to RMT-mediated drug delivery through Fc region engineering. Modifying the impact on endogenous ligands and regulating antibody distribution and persistence in peripheral tissues via engineered Fc receptor interactions.

RMT-Targeting Peptide Optimization

Our expertise in medicinal chemistry-based peptide optimization allows us to generate RMT-targeting peptide variants with a broad range of biological properties using techniques such as alanine scanning, D-amino acid scanning, truncations, cyclization, and the incorporation of non-natural amino acids.

RMT-Targeting Vector Validation Services

After optimization, it is critical to robustly validate RMT-targeting vectors to confirm BBB penetration and biological activity. Ace Therapeutics uses a variety of techniques to evaluate brain uptake of antibodies or peptides targeting RMT systems.

Services	Description
Discerning parenchymal versus endothelial uptake of RMT-targeting vectors	We use capillary depletion or fluorescence-activated cell sorting (FACS)-based isolation methods to help clients distinguish the antibody or peptide that is bound to or internalized into the BBB endothelium versus that which has undergone full transcytosis into the brain parenchyma.
Measuring pharmacodynamic (PD) responses of RMT-targeting vectors	We help clients evaluate the ability of RMT-targeting vectors to deliver pharmacologically relevant doses of therapeutic cargos by using PD analyses in wild-type animals and disease models, such as rodent Alzheimer's disease models, rodent stroke models, rodent Parkinson's disease models, rodent models of lysosomal enzyme disorders.

Our Advantages

Deep Expertise in Brain Drug Delivery

Our team has extensive experience in RMT biology, BBB transport mechanisms, antibody engineering, and peptide optimization.

Custom RMT-Targeting Vector Optimization Solutions

We can develop RMT-targeting vectors that can bind to both non-human and human forms of the target receptor, and optimize them to generate variants with unique properties.

Rapid Turnaround and Collaborative Support

We offer dedicated project managers, transparent timelines, and collaborative consultation to help you meet your program goals efficiently.

At Ace Therapeutics, we are committed to helping our clients develop more effective RMT-targeting vectors that can be coupled with drugs and transported across the BBB. We strive to be your trusted partner in overcoming BBB drug delivery challenges. Contact us today to learn more about our RMT-based strategies for delivering drugs to the brain.

Reference

Lajoie, J. M., & Shusta, E. V. (2015). Targeting receptor-mediated transport for delivery of biologics across the blood-brain barrier. Annual review of pharmacology and toxicology, 55(1), 613-631.