Preclinical Design and Development Core

Developing therapeutics for children with ultrarare diseases is not considered commercially viable and thus lies outside the scope of traditional pharmaceutical companies. Through the GEMINI program, St. Jude brings innovative precision medicine approaches into the clinic to treat patients with neurological disorders, thus establishing St. Jude as a foundational leader in addressing this critical unmet need for catastrophic pediatric neurological diseases.

The PDD Core works to develop, operationalize and optimize the ASO development pipeline at St. Jude. By integrating patient-derived models with targeted molecular design and comprehensive screening efforts, preclinical development of therapeutic candidates can be tailored to the patient’s genetic profile. This process is designed to bridge the gap between genetic diagnosis and therapeutic intervention, supporting the GEMINI program’s broader mission to deliver individualized treatments.

To increase throughput and improve reproducibility, the PDD Core is implementing an automated liquid handling system to support functional screening of antisense oligonucleotides (ASOs). This transition is enabled by advanced high-throughput robotic platforms, including the JANUS G3 Expanded systems (8-tip + MDT, RUO; and MDT, IVD configurations), which collectively support scalable processing of more than 500 oligonucleotide candidates per patient-derived cell line. This automation enhances assay consistency, reduces manual variability and enables systematic expansion of individualized RNA therapeutic development across a growing number of cases.

Dr. Rachayata Dharmat received her PhD from Baylor College of Medicine (BCM), where she trained in cell and molecular neurobiology, mouse genetics and neural development with an emphasis on neurological disease. Before leading the PDD Core, she was a postdoctoral fellow with Dr. J. Paul Taylor in the Department of Cell and Molecular Biology.​ Dr. Dharmat has expertise in neurological disease modeling, gene discovery and functional genomics, with a strong interest in developing therapeutic approaches for neurological disorders. From her role as an initial team member at the BCM Single Cell Genomics Core, she has expertise in establishing core standard operating procedures (SOPs) and providing high-quality research support.​ As director of the PDD Core, Dr. Dharmat is establishing the preclinical pipeline for the development of individualized genomic therapies through the St. Jude Pediatric Translational Neuroscience Initiative’s GEMINI program, initially focusing on antisense oligonucleotides.​