SpliceCore Discovery Applications
Antisense Drugs
Target discovery and compound design
Antisense drugs, or antisense oligonucleotides (ASO), are synthetic RNA molecules that modify the intracellular synthesis of disease-causing proteins by binding to the RNA error responsible for their formation.
Antisense drugs are the most direct way to selectively target and correct RNA splicing errors, making them potentially safer than traditional drugs.
We can design an ASO rationally and manufacture them rapidly because we can predict the coding sequence of the target RNA
Neoantigen Detection
RNA splicing driven neoantigens for immunotherapy
Neoantigens are novel peptide fragments in tumors that can activate the body’s immune system to attack the cancer and eliminate it.
These are tumor proteins that are processed into 8 to 11 residue peptides by proteasomes, then shuttled into the endoplasmic reticulum by transporters and loaded on MHC for recognition by T-cells.
We have developed a novel approach to identify neoantigens from RNA sequencing data which are invisible to classical DNA-based approaches. Our neoantigen discovery pipeline identifies tumor specific alternatively spliced proteins that can be processed into peptides with MHC-binding affinity and potential to induce T-cell response. This results in fast detection of splicing-derived tumor-specific neoantigens for immunotherapy.
Biomarker Discovery
Clinical biomarkers for patient stratification
Cell surface receptors, such as HLA, are proteins embedded on the surface cells that are used as binding targets for immunotherapy antibodies.
RNA splicing errors can alter the structure of these proteins and affect the ability of antibodies to bind to cell surface receptors.
Profiling cell surface receptor structures can improve drug design and effectiveness.
We analyze RNA sequencing to profile receptor splicing variation and with our validated in-vitro pipeline can identify biomarkers and stratify patients in less than 2 years.
