Frequently Asked Questions

Mission & Impact

  • We are building a more efficient model for drug development to treat rare diseases previously overlooked due to high financial risk of drug development. Thanks to new computational tools, we are now able to unravel molecular similarities in disease pathology and treatment response regardless of the clinical diagnosis or root cause, but we need additional data representing as many of the 10,000+ rare disorders as possible to do this. We are creating a centralized database and drug discovery platform to collaboratively drive the discovery of therapeutics that benefit more than one orphan disorder at a time, for disorders caused by genetic changes from a single gene all the way to whole chromosomes and of unknown/undiagnosed origins. Through rareSHIFT™, Unravel is offering services through its drug discovery platform that can identify repurposed drug candidates and develop them all the way through clinical proof of concept trials.  

  • RareSHIFT™ enables researchers to leverage RNAseq data towards developing new therapeutics for ultra-rare disorders that traditional pharma overlooks. Lack of access to relevant data creates a bottleneck and limits the rate at which researchers and drug developers can discover new therapeutics. RareSHIFT™ aims to generate and mobilize RNAseq datasets to anyone interested in freely using this data for biomedical research, including research groups you may already be supporting. Additionally, Unravel’s discovery platform is now available for families and foundations to meet their repurposing and new target/drug development needs. 

  • In addition to serving as a source of data for research, Unravel Biosciences is making drug discovery and development more efficient, including new and repurposed drugs. Reports from each study are shared with the participants to provide personalized analyses of their condition as well as possible drug repurposing candidates that can drive additional research. Unravel has already identified two existing drugs that will soon enter four separate clinical trials, including the first ever for a particular orphan neurodegenerative disorder. By identifying shared therapeutic responses among unrelated rare disorders, Unravel is finding opportunities for multiple foundations to syndicate resources to more efficiently support drug development. Our partners have expertise in conducting clinical trials in rare pediatric neurological disorders and provide an opportunity to quickly translate potential candidates to the clinical. Together we are accelerating the discovery of therapeutics that will benefit multiple patient populations at once.   

    *PLEASE NOTE THAT WE DO NOT PROVIDE DIAGNOSTIC OR THERAPEUTIC SERVICES. ALL DATA AND REPORTS ARE INTENDED FOR RESEARCH USE ONLY.  

  • Unravel Biosciences harnessed patient RNA data to uncover a promising breakthrough for Rett Syndrome in just one year, discovering a new therapeutic mechanism that can be engaged using an existing prescription drug. The discovered novel therapy surpasses the only approved drug in mouse models and is poised for upcoming clinical trials. Unravel has repeated this approach with other neurodevelopmental and neurodegenerative disorders, including saving months of screening by analyzing RNA with the BioNAV discovery engine. Additionally, multiple patients have opted to use the generated data and drug hit lists to work with their clinical teams to evaluate drugs off-label and have found promising results. As an example of how robust the approach is, Unravel’s lead drug prediction for a neurodegenerative disorder, generated and validated in under one year, has been nominated for the supporting foundation’s very first clinical trial. We are partnered with multiple foundations to develop custom repurposing and target discovery programs based on patient RNAseq data and enabling clinical trials in rare and ultra-rare disorders. RareSHIFT™ will amplify this impact exponentially! See Unravel’s science here. 

Platforms

  • Therapeutics are currently developed to treat a specific indication, or diagnosis. However, we already know that a drug developed to treat one disease can be used to treat another. Clinicians also know that similar symptoms or even an identical diagnosis between two patients does not mean they will both be treated by a drug approved for that disease. Unravel has developed the concept of a Therapeutic Responder Group to stratify or cluster patients using Unravel’s proprietary AI algorithms and patient RNA signatures based on potential treatment response rather than the root cause of a disorder. No matter if the disorder is caused by a single gene, multiple genes, or genetic and environmental factors, Therapeutic Response Groups are used to find shared ways to treat them.  

  • Although DNA sequencing of the genome has gotten far more attention, RNA tells a different story. DNA mutations are mostly unchanged over the life of a patient. RNA on the other hand tells a dynamic story of each patient’s specific condition, not just the genetic contributions of their entire genome but also the impact of their environment, sleep, diet, medications, activity, and even the microbiome. As a patient’s disorder progresses or is treated, RNA keeps informing on what is happening. Even for disorders with clear disruption of proteins, RNA still provides a view of the biological system, offering strategies for treatment. The historical lack of RNA data, unlike DNA data, is a major motivator for creating this database.   

  • A variety of cells – including epithelial, immune, mucosal gland, nerve, etc. – are found in the nostrils. Our nasal swabs capture 57,000+ coding and non-coding transcripts. In addition, they provide reliable coverage of all 1,600 neuronal and synaptic genes, as well as neuronal-related pathways. We also see pathways relevant to most other disorders as epithelial, connective, immune, and vascular tissues are collected in the process. 

    *PLEASE NOTE THAT WE DO NOT PROVIDE DIAGNOSTIC OR THERAPEUTIC SERVICES. ALL DATA AND REPORTS ARE INTENDED FOR RESEARCH USE ONLY.  

  • BioNAV™ was trained using data from an assortment of cell lines, including cancer lines, that were manipulated to over- or under-express a single gene. While there are cell-specific differences, this approach enabled us to identify conserved probabilistic networks. Additionally, the drug database was created using mostly cell lines to generate the data. We were able to overcome the specificity problems by identifying overarching drug effects. This means we are likely missing the context-specific effects in our analysis, but it also means that the predicted mechanisms/drugs are much more likely to translate across preclinical models and into patients. In essence, we are okay with false negatives as long as we find some effective drugs. 

  • In the SquishyWare™ model, we use CRISPR editing to knock down genes or induce missense and other mutations at one or more sites across one or more genes. While there is generally good evolutionary conservation in sequence and function, we can also humanize the model by injecting mRNA for any desired gene/sequence. This also enables us to work with gain-of-function mutations and complex genetic scenarios. 

    We also frequently work with established models as available, including through our collaboration with Jackson Laboratory and correlate model’s drug responses with that of patients to best align preclinical models to the patient populations. 

  • We see consistency in drug predictions for cases where we resampled the same individual. Normally this occurs over a span of several months, but we see pathways corresponding to drug treatment shift in response while other pathways remain fairly unchanged. In personalized studies, we collect RNA over 8 time points across 2 days. This serves to handle the natural changes in expression due to circadian rhythms. 

  • We are waiting to compare the results of this study, comparing blood to nasal swab samples collected at the same time. Samples are being sequenced, and this is in studies with humans and, separately, in sea lions. We fully expect gene expression baseline and differential changes to be quite different between tissues. We however expect the drug predictions to be highly correlated, as we have seen from other studies with different tissue types (and even species), such as in our statin and COVD-19 publication: Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients

  • If someone’s state of health can represent the patient’s desired state of health, then they can be considered the healthy control. This is because, in layman’s terms, BioNAV™ predicts molecules that will make the patient more like the control.  

Procedures & Legal

  • We believe in supporting rare disease scientific research. By generating often, the very first clinical molecular datasets for rare disorders, we are committed to facilitating additional research programs. All resulting de-identified data will be shared with participants for research and clinical use. In parallel, Unravel will process the data using its AI analytical platform to predict potential Therapeutic Response Groups and shared drug targets to make rare disease therapeutic development massively faster and less expensive.  

  • RareSHIFT™ is building on the effort of clinical researchers who banked specimens under appropriate and valid human subject protocols overseen by an Institutional Review Board (IRB) that permit sharing of deidentified data for research purposes while providing strict privacy and confidentiality protection to participants. We offer new sample collection using our proprietary nasal swab RNAseq method under an existing IRB protocol and are happy to continue to support your drug development and clinical translation strategy.  

  • Absolutely! Patient identifiers, including genetic sequence data and Protected Health Information, will be removed by us or our clinical research institutional partners as per IRB protocol guidelines prior to any data sharing or publication.  

    *PLEASE NOTE THAT WE DO NOT PROVIDE DIAGNOSTIC OR THERAPEUTIC SERVICES. ALL DATA AND REPORTS ARE INTENDED FOR RESEARCH USE ONLY.  

  • Unravel contracts with foundations/families through a template service agreement to enable RNAseq data generation, in silico drug screening, and potentially animal model development and screening. Unravel’s mission is to develop effective therapeutics in a collaborative manner. To that end, we charge families and nonprofit foundations only what it costs us to perform the work and in return own resulting intellectual property to enable long-term drug development, including for new formulations of existing drugs as well as entirely new molecules. For drug repurposing and other programs, we offer standard services and custom studies depending on scope and needs. Request a customized quote here.