ROME is designing therapies with the potential to modulate disease at the source. We are pursuing drug discovery and development by targeting three disease-relevant consequences of repeat dysregulation.
We are developing novel therapeutics that block repeat-induced proinflammatory responses.
We are developing novel therapeutics that specifically target cancer cells expressing abnormally high levels of repeat-derived antigens.
We are developing novel therapeutics targeting repeat-induced genomic instability that drives cancer progression.
Blocking LINE-1 reverse transcriptase in autoimmune disease
LINE-1 in Autoimmune Disease
LINE-1 is a ubiquitous family of transposable elements embedded in the dark genome. The human genome contains roughly 500,000 copies of LINE-1, about 100 of which are active and encode a functional reverse transcriptase (RT).
When aberrantly expressed, LINE-1 RT copies RNA into DNA in the cytosol, triggering a viral mimicry response via nucleic acid-sensors. This results in activation of Type 1 interferon and NFkB pathways that drive autoimmune disease pathology.
ROME’s LINE-1 RT Inhibitors
Through rational structure-based drug design, ROME has identified novel, selective and potent inhibitors of LINE-1 RT. Preclinical data show that ROME’s compounds inhibit Type 1 interferon responses in multiple models of autoimmune disease.
LINE-1 reverse transcriptase is not expressed in healthy cells, providing a unique opportunity to specifically target diseased cells. Unlike the broad activity of immunosuppressants, LINE-1 RT inhibitors are designed to selectively block pathogenic interferon signaling without affecting host defense.
Our data science platform
Our data science platform is designed to illuminate the target-rich yet underexplored dark genome, using proprietary tools and algorithms to identify and advance new and better therapies. High-resolution mapping and annotation techniques first identify functionally active repeats, then machine learning methods quantify their expression to determine which of the mapped repeats are driving disease. The platform has shown demonstrated capabilities in target discovery and indication selection; it can also inform clinical trial design, biomarker discovery and potentially provide a means to measure an individual patient’s response to therapies.
ROME’s data science platform is the first and most comprehensive set of unified genomic analysis tools to specifically probe the repetitive elements and their function. Using conventional approaches, it is easy to inaccurately estimate the abundance of repeat-related activities since the sequences of functional and nonfunctional repeat elements are often very similar to each other. Our platform has been tuned to focus on the individual repeats that are active, yielding insights about activities within the cell that drive disease.
High resolution map of annotated repeats in the human genome
We have mapped and curated human repetitive elements at a high resolution, creating the largest existing database of annotated functional repeats. This database, called ROMEMap, stores detailed information for millions of repeats. These data can be used to identify new targets for drug discovery, understand differences between individuals and serve as a precise reference for expression quantification.
Measures expression of active repeats
ROMEQuant uses machine learning methods to quantify repeat expression and determine which repeats are active. This is a crucial step in determining which repeats are associated with disease and in identifying biomarkers for distinct indications or patient populations.
ROME has deep expertise in the biology of genomic repeats and specialized repeat-oriented data science tools with a variety of applications. We are open to and interested in applying these capabilities in new settings through strategic collaboration.