rareSHIFT is Unravel Biosciences' drug discovery platform for rare disease patients. It analyzes each patient's RNA profile (collected via a simple nasal swab) using a validated computational model (BioNAV) to rank existing molecules — drugs and supplements — by how likely they are to shift the patient's biology toward a healthier state, usually their first degree healthy relative as a control. The platform rests on the idea that molecular similarities in disease pathology and treatment response can be found across different rare disorders, regardless of clinical diagnosis or genetic root cause, so that therapeutic development can benefit more than one orphan disorder at a time. Top candidates are reviewed with families and clinicians and can be validated further in vivo if needed. 

Considerations: This is for research use and not intended as a treatment recommendation. Typical timeline for personalized results is about 4-6 weeks but rush options are available. Results are agnostic to genetic diagnosis, comborbidities, or lack of diagnosis. 

Unravel's platform uses a network biology approach, analyzing entire systems and pathways together rather than single genes. While gene expression varies greatly from tissue to tissue, we have found that mechanisms for restoring the network are relatively conserved across the body. This allows BioNAV™ to infer, from one tissue source, how to potentially address a genetic perturbation reflected elsewhere in the body. Nasal tissue is not strictly required — Unravel can work with other tissue samples — but nasal swab collection is what falls under Unravel's existing IRB protocol; any other tissue collection would need to be arranged independently or through a custom research protocol. Nasal swabs are also used because the preservation solution we use inactivates pathogens to simplify international shipping, reaching patients worldwide. 

Nasal swabs, self-collected at home at multiple timepoints across 48 hours, from the patient and one healthy first-degree relative serving as control. Kits include instructions and pre-paid return shipping. Unravel also works with patients with episodic symptoms to collect samples over appropriate time periods to inform on the patient’s biological state and use the patient as their own control. Further customization is available. 

Considerations: Controls should be symptomatically healthy; swabs should be collected during stable health (no acute illness or recent medication changes). 

Predictions come from a large perturbation database and a validated pipeline; clinicians and families have reported meaningful clinical responses in multiple cases, and in-vivo models have validated many top predictions. Unravel filters candidates for factors like safety during report generation and uses its SquishyWare (tadpole-based) platform to help validate top candidates for safety and efficacy. Underlying data is also shared back so partners can independently test candidates in existing models. 

Considerations: Not every candidate works for every patient — results are individualized, and while promising, success is variable. No drug is inherently “safe” in isolation; dose materially affects the risk/benefit picture. Determining appropriateness for a specific patient, including any off-label use, is ultimately the responsibility of that patient's treating clinician. 

Reports contain many drug candidates to select from, giving far more than one option. Unravel offers resampling and re-analysis (shorter time and lower-cost than the original study) to monitor a patient's molecular response over time and help guide next choices; families can work through the ranked candidate list with ongoing clinical oversight and the Unravel team available as needed for consultation.