On Thursday, May 28th, 2020, Lucerna will be giving a virtual talk to present the latest advances in its high-throughput RNA splicing drug discovery platform at the 25th Annual Meeting of the RNA Society. Due to the COVID19 pandemic, this year’s RNA Society meeting will be held complete on-line this year. Therefore, Lucerna’s presentation will be available for viewing at the following time:
Title: Spinach splice sensor: a cell-based drug discovery platform for splicing-related diseases
Presenter: Karen Wu, Ph.D.
Workshop 3: Targeting RNA for Therapy and Diagnostics
Date: May 28, 2020
Time: 4:30 – 6:00 PM Eastern Time (and 72 hours afterwards)
RNA splicing plays a central role in the generation of proteome diversity and in gene regulation. Splicing affects cellular processes, such as cell-fate and differentiation, acquisition of tissue-identity, and organ development. For human diseases, it is estimated that up to 50% of all pathogenic genetic mutations may affect RNA splicing. Additionally, defects in splicing are linked to spinal muscular atrophy, Duchenne muscular dystrophy, Parkinson’s disease, and several types of cancer. Recent studies with drugs modulating RNA splicing have demonstrated potential as effective therapeutics for these diseases, and subsequently intensified efforts for drug discovery of novel spliceosome targets. However, monitoring RNA splicing with current techniques (RT-qPCR and RNA-seq) are not readily adaptable for high-throughput screening (HTS) and is cost-prohibitive at this scale due to their complex and time-consuming methodology. While splice mini-gene systems are higher throughput, they lack the ability to monitor the endogenous target RNA due to its artificial design. Thus, there is an unmet need for simple and robust cell-based, HTS-ready assays to monitor bona fide endogenous RNA splicing.
To address this critical bottleneck for splice modulation drug discovery, Lucerna has developed a simple, HTS-ready splice sensor platform that can be customized to detect any splicing event of interest. In our assay format, sensor reagents are added to target cells in one step and read at room temperature in common fluorescent plate readers. This homogenous workflow significantly reduces sample handling time and error rates compared to other competing assays. Importantly, the assays can detect as little as 10% splicing changes which impacts false negative hit rates and increase viable hit identification.
Here we show splice sensors against survival motor neuron 1, pyruvate kinase isoforms, and splicing targets involved in neurodegenerative diseases. Further, we have adapted the splice sensors into cell-based assays capable of detecting endogenous RNA isoform changes caused by small molecules or siRNA perturbations. This allows the use of more disease relevant materials, such as patient-derived primary cells and total RNA from tissues extracted from in vivo models. In summary, the Spinach splice sensor platform offers HTS-ready, disease-relevant, and customizable assays for better splice modulating drug discovery.
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Lucerna, Inc. aims to be the industry leader in the development of RNA-based research and drug discovery reagents. Its motto of “making all RNA visible and druggable” reflects Lucerna’s mission to develop plug-and-play products that allow better imaging and detection of RNA, and high-throughput screening platforms that enable new drug discovery of previous intractable RNA targets. Based on exclusive worldwide rights to groundbreaking research from the laboratory of Samie R. Jaffrey, M.D., Ph.D., at Weill-Cornell University, Lucerna has generated a collection of intellectual property, know-how, and trade secrets to strengthen its market position in this newly burgeoning RNA field. Through innovation and alliances, Lucerna plans to expand its product offerings into areas related to RNA-targeted therapeutics, epitranscriptomics, biomarker detection, and single-cell analysis. Lucerna is a privately held company headquartered in Brooklyn, NY. For more information about Lucerna, please visit lucernatechnologies.com.