The Center for Rare disease models (CRDM) has been set up in order to create Rare disease models of inherited monogenic diseases prevalent in India and to facilitate therapeutic discovery. A repository of these models will also be maintained at the center and made available for use under various modes.
Infrastructure upgradation
As part of the new CoE, a new facility capable of performing targeted genetic engineering in zebrafish and/or cell lines has been set up. Dedicated laboratory space was upgraded and equipped with the following state-of-the-art facilities: Semi-automated Zebrafish housing system; Deep Freezer for line cryopreservation; BSL2 Cell Culture Facility; High-throughput Imaging Station, Fluorescence-based Cell Sorter, Protein Purification system, and Nanopore-based Next-generation Sequencing.
Model Development
Generation of genetically engineered models of rare diseases noted as a significant burden among the Indian population. Using Advanced Genetic Engineering technology (CRISPR), a novel zebrafish model of Duchenne Muscular Dystrophy (DMD) was generated by mutating the dystrophin gene. These mutant zebrafish show features of human DMD, mainly characterized by decreased locomotion abilities, and loss of muscle structure. A provisional patent application is being filed claiming the features and utility of this model, and a research article is being submitted to report the findings. In addition, this model has been used to screen DMD drug candidates discovered by an Indian Biotech startup company. In addition to DMD, other rare disease models in zebrafish and cell lines are being developed.
Repository Establishment
Workflows have been established for cryopreservation of zebrafish sperm and cell lines to serve as a repository of rare disease models.
Training and Outreach
Students and post-doctoral scientists have received training in the above methods and technology platforms. Outreach efforts have resulted in expression of interest from several organizations including academia and industry, leading to utilization of the DMD model for drug screening as mentioned above.