AbDrop™: The Future of Fast, Fully Human Antibody Development
Introducing a new High-throughput Fully Humanized Antibody Discovery Platform with Biointron AbDrop™ & Cyagen HUGO-Ab™! This novel approach combines microfluidic technology for single B cell antibody discovery and fully human antibody mice for a safer and more efficient approach for fully human antibody discovery, ready in as quickly as 3 months.
Traditional monoclonal antibody (mAb) discovery methods often rely on animal-derived or humanized antibodies, which require additional modifications to reduce immunogenicity. Fully human antibodies overcome these limitations by minimizing unwanted immune responses, making them more suitable for therapeutic applications. With advancements in high-throughput screening technologies and genetically engineered mouse models, fully human antibody development has become faster, more efficient, and more precise.
How HUGO-Ab™ Mice Enable Fully Human Antibody Production
The process begins with animal immunization using HUGO-Ab™ mice, which are genetically engineered to produce fully human antibodies using TurboKnockout® ES technology. This technology replaces the endogenous VH and VL genes by fully human VH and VL genes in situ to offer more stable phenotypic and functional outcomes in progeny compared to traditional transgenic methods. Humanizing the whole heavy and light chain V(D)J variable regions offers greater genetic diversity and low immunogenicity for antibody development, in addition to a more diverse antibody repertoire generation from V(D)J recombination to ensure an immune response like that of wild mice when exposed to antigens.
In contrast to traditional transgenic mice that introduce large artificial gene segments, HUGO-Ab™ mice utilize in situ gene replacement, ensuring that humanized antibody genes are expressed under native regulatory elements. This results in a more natural immune response, closely resembling wild-type mice.
TurboKnockout® ES Technology: Enhancing Genetic Stability and Diversity
TurboKnockout® gene-editing technology based on embryonic stem (ES) targeting retains the advantages of traditional ES targeting such as maturity, precise modification, and stable results. It works by microinjection at specific embryonic development stages, so TurboKnockout® ES cells can completely replace endogenous ES cells. Therefore, we bypass the "chimeric" stage and shorten the ES targeting production cycle to as short as 4 months, reducing the breeding time by two generations. This makes it the preferred method for constructing complex models, such as those requiring large segment gene modifications.
Unlike CRISPR-based knock-in strategies, which may lead to unpredictable gene expression due to random insertions, TurboKnockout® ES technology ensures precise, targeted replacement of antibody variable gene regions. This results in stable genetic expression across generations, reducing variability in antibody responses.
Related: Antibody Humanization
AbDrop™: High-Throughput Antibody Screening with Microfluidics
Biointron's AbDrop™ platform leverages microfluidic technology as the screening method to generate droplets encapsulating individual plasma cells. Once the B cells are collected from the mice, each single B cell will be encapsulated with a labeled antigen and a labeled secondary antibody in a macro-droplet. FRET fluorescence is induced so the chip can sort positive droplets, which will then be emulsified to release the cells for sequencing. Screening and enrichment of 1-2 million plasma B cells can be completed within a single day, and hundreds of naturally paired heavy & light chains are obtained at a single time. Afterward, NGS sequencing, high-throughput expression and validation, and data analysis will be conducted in one week, and overall, it will take one month from screening to purified antibody candidates with validated activity.
Since the AbDrop™ platform can screen 1-2 million plasma B cells in a single day, this significantly outperforms traditional hybridoma techniques, which may take weeks. Additionally, the use of FRET-based fluorescence sorting enables precise selection of antigen-specific B cells, leading to a higher hit rate and a more diverse pool of antibody candidates.
Advantages of Microfluidic Technology for Antibody Discovery
Microfluidic technology for antibody development involves manipulating small fluid volumes within microfabricated channels, offering precise control over experimental conditions and enabling high-throughput testing. This technology reduces reagent consumption, enhances reaction kinetics, and integrates multiple development steps into a single device, improving efficiency, speed, and precision in antibody production and screening. Compared to other single B cell technologies, AbDrop™ has several advantages:
By minimizing reagent consumption and enabling high-throughput single-cell analysis, microfluidic platforms provide a more cost-effective and scalable solution for therapeutic antibody discovery. Compared to hybridoma technology, which relies on labor-intensive cell fusion and expansion, microfluidics rapidly isolates and screens functional B cells in their native state, preserving natural heavy-light chain pairing.
Related: Single B Cell Screening
Why Use Us?
Fully human antibodies now represent a significant portion of FDA-approved biologics, with blockbuster drugs such as Adalimumab (Humira®) and Nivolumab (Opdivo®) demonstrating the therapeutic potential of these molecules. The ability to rapidly generate diverse, high-affinity antibodies through advanced platforms like HUGO-Ab™ and AbDrop™ is paving the way for more efficient therapeutic development pipelines.
Our High-throughput Fully Human Antibody Discovery Platform eliminates the need for complex modifications and simplifies the development process, reducing costs and accelerating the discovery of safer and more effective antibody drugs. To learn more, visit the service page here, or contact our expert team at info@biointron.com, or by phone at +1(732)790-8340.
