RD – Factory

ACCELERATING SOLUTIONS FOR RARE DISEASES FROM THE LAB TO THE CLINIC

While individual rare diseases (RD) affect relatively small populations, their collective impact is profound, touching the lives of over 300 million people worldwide. Despite this massive burden, the vast majority of these conditions lack approved therapies. To address this critical gap, the Czech Centre for Phenogenomics (CCP) has established the RD-Factory, a strategic initiative designed to function as a comprehensive ecosystem for the functional analysis and treatment of rare genetic variants.

The RD-Factory program at CCP is a strategic, long-term initiative designed to accelerate the understanding, diagnosis, and treatment of rare genetic diseases by tightly integrating advanced mouse modelling, deep phenotyping, and translational expertise with the needs of clinicians, researchers, patients, and patient organizations. Building on CCP’s experience with more than 1,000 mouse models and the drug- and biomarker-development capacity of the Institute of Molecular and Translational Medicine (IMTM), RD-Factory focuses on creating and exploiting disease models, especially for cell and gene therapies and repurposed compounds, with the clear ambition of moving promising concepts toward preclinical testing and, ultimately, clinical application.

A defining strength of the RD-Factory program at CCP lies in the close interaction between genome engineering and animal model production on one side, and a deeply integrated phenotyping and translational team on the other. The phenotyping platform was originally developed within the framework of the International Mouse Phenotyping Consortium (IMPC), with a strong emphasis on data reproducibility and robustness. As technologies have evolved and new societal and clinical needs have emerged, these operational capabilities are now being directly applied to the characterization of pathogenic variants in human genes, the testing of therapeutic interventions, and preclinical development. Such integration goes far beyond standard model characterization. It enables a deep pathophysiological understanding of disease mechanisms through the combination of advanced and highly focused testing across physiological and developmental levels within a single, coordinated workflow. Equally important is the use of sophisticated phenotyping pipelines that allow preclinical data to be closely aligned with clinically relevant endpoints. This level of integration makes it possible to conduct robust proof-of-concept studies and precisely designed efficacy trials, ensuring that preclinical findings are not only biologically sound but also directly translatable to human patients.

The program distinguishes itself by offering a complete “one-stop shop” that connects the initial genetic discovery directly to preclinical solutions. The process begins with a collaborative nomination system, inviting researchers, clinicians, and patient advocacy groups to submit specific genes or variants suspected of causing disease. Once a target is prioritized, CCP leverages its state-of-the-art infrastructure to generate precise disease models.

Since its launch, RD-Factory has established an open, continuous call for nominations of genes and diseases that invites contributions from clinicians, scientists, rare-disease experts, patients, and patient organizations, ensuring that the project pipeline reflects real unmet medical needs rather than purely academic priorities. In the first nomination round, which closed in December 2024, 45 genes and diseases were submitted and evaluated by experts from CCP and IMTM, resulting in the selection of 11 high-priority proposals, significantly more than initially planned, thanks to synergies with existing CCP activities and the International Mouse Phenotyping Consortium. The selected portfolio includes disorders such as ADSL deficiency, Pitt Hopkins syndrome, Canavan disease, Bloom syndrome, and several developmental and epileptic encephalopathies, alongside other neurodevelopmental and metabolic conditions, representing a curated set of rare diseases that are seriously under-researched worldwide but clinically urgent.

​On this basis, CCP and IMTM have already launched concrete research and development projects for several rare diseases under the RD-Factory umbrella, including Netherton syndrome, Angelman syndrome, Prader–Willi syndrome, SPATA5 syndrome, Diamond–Blackfan anemia, autosomal recessive congenital ichthyosis, cystic fibrosis, and hereditary or otherwise rare cancers. These projects make use of cutting-edge gene editing, sophisticated in vivo phenotyping, omics platforms, and imaging technologies to dissect disease mechanisms and establish robust models suitable for therapy testing. The work is embedded in CCP and IMTM’s certified environments (GLP, ISO 17025, ISO 15189), which enables regulatory-grade preclinical and diagnostic development and positions selected RD-Factory projects for later translation into clinical trials.

Success in this challenging field requires a united front, which is why the initiative operates in close partnership with the Institute of Molecular and Translational Medicine (IMTM) for high-throughput drug screening and the Rare Diseases Czech Republic (ČAVO) to ensure patient perspectives guide the research. By integrating our technologies with a patient-centric approach, the RD-Factory is actively accelerating the translational journey from laboratory bench to bedside.

For more details on the RD – Factory program see: https://www.phenogenomics.cz/rare-diseases/