Shanghai Immunocan Biotech Co., Ltd. (“Immunocan”) today announced the successful in situ replacement of megabase (Mb)-scale human immunoglobulin (Ig) gene segments at endogenous Ig loci in rabbits using its proprietary MASIRT® (Massive-fragment Across Species In situ Replacement Technology) platform.
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A MASIRT®-Engineered Humanized Rabbit Platform for Fully Human Antibody Discovery
Genotypic characterization confirmed targeted, single-step replacement with the human sequences. Unlike conventional transgenic approaches that often rely on random integration, MASIRT® enables precise engineering of large human gene segments at endogenous loci while preserving their structural organization and regulatory elements.
This milestone extends Immunocan’s genetic engineering capabilities from mice to rabbits, establishing a foundation for a rabbit-based human antibody discovery platform and demonstrating the cross-species applicability of MASIRT®.
Rabbits Expand Antibody Discovery Against Challenging Targets
Rabbits have distinct immune responses and antibody repertoires compared with mice. They can generate antibodies against epitopes that are poorly immunogenic in rodents or highly conserved across species, potentially expanding sequence and epitope diversity for challenging targets.
Rabbit-derived antibodies may also recognize conserved epitopes shared by human and mouse proteins. When experimentally confirmed, such cross-reactivity can support efficacy studies in wild-type mouse models, potentially reducing the need for target-humanized animals.
These properties may be particularly valuable for complex targets such as ion channels, transporters, and other multi-transmembrane proteins, which often present limited accessible epitopes. Rabbit-based human antibody discovery could offer new opportunities for targets that have been difficult to address using conventional approaches.
Building a Multi-Species Antibody Discovery and AI Platform
The rabbit milestone builds on Immunocan’s established mouse portfolio, including ImmuMab® for fully human antibodies, ImmuMab Light® for common light-chain antibodies, and ImmuMab Heavy® for heavy-chain-only antibodies.
These platforms support antibody discovery through hybridoma and phage display technology, single-B-cell screening, and NGS- and single-cell-sequencing-based clonal family mining. A typical program can generate hundreds to thousands of target-binding fully human antibody sequences for lead identification and preclinical candidate nomination.
Immunocan has established partnerships with more than 30 pharmaceutical companies worldwide, including multinational corporations. By combining its established mouse platforms with its developing rabbit model, the company aims to broaden antibody diversity and create new opportunities for platform partnerships and licensing collaborations.
The cross-species strategy also supports Immunocan’s AI-enabled antibody discovery efforts. Its humanized mouse platforms have generated hundreds of millions of data points, providing valuable resources for training, evaluating, and refining AI models. Combining experimental data from mice and rabbits may help AI models learn from broader sequence–function relationships, supporting future epitope prediction, sequence design, and developability assessment. These capabilities will require iterative training and validation against experimental results.
Next Steps
Immunocan will continue evaluating the integrity, rearrangement, and expression of the introduced human gene segments, confirm germline transmission through breeding, and assess immune function and discovery performance across diverse target classes.
The company also plans to explore rabbit models supporting heavy-chain-only (HCO), common light-chain (CLC), and multispecific antibody discovery. These efforts aim to expand options for challenging targets and support future AI model development.
The successful Mb-scale replacement marks a major milestone in Immunocan’s cross-species engineering program, laying the foundation for broader antibody discovery applications and future collaborations.
About Immunocan
Founded in 2020, Immunocan specializes in gene-editing technology to replace immunoglobulin variable-region genes in animals, enabling the development of genetically engineered models capable of producing fully human antibodies and other innovative modalities. The company provides antibody discovery platforms to drug research partners worldwide, with the goal of developing safer and more effective treatments for human diseases.
For more information, visit https://immunocan.com/.
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