Lucerna has received a 1 year $225K SBIR Phase I grant from the National Institute of Allergy and Infectious Diseases to develop new high-throughput screening (HTS) platform to enable better anti-viral drug discovery. There is currently a lack of robust screening tools that offer cell-based target engagement, especially in antiviral drug discovery . Therefore, Lucerna aims to develop a HTS assay that reports endogenous viral polymerase activity, as well as off-target drug activities, in living cells. The ultimate goal of this project is to expand our portfolio of drug discovery platforms by utilization our Spinach technology to develop cell-based HTS assays against most important RNA viruses.
Abstract
Our goal is to develop a new cell-based HTS platform that can be used to improve antiviral drug discovery. Infection by Dengue virus causes 100 million illnesses annually with outbreak severity and frequency increasing with time. This is true of all RNA viruses, which includes Zika, Ebola, Influenza, Yellow Fever, and Hepatitis C, to name a few. In addition to the health burden Dengue alone represents, dengue fever constitutes a large global financial burden (39 billion USD), and with 20% of the world’s population living in at risk areas there is an urgent need for dengue therapeutics. There is currently no approved universal vaccine or dengue specific antiviral drug. Current antiviral drugs on the market target viral enzymes; viral enzymes often have structures that are not present in mammalian cells and are absolutely required for their life cycle making them good targets. High-throughput screening assays for dengue drug discovery are either performed in vitro or in vivo. In vitro assays are target specific but results do not translate well when performed in cells. In vivo assays are more clinically relevant but the target of the drug is unknown making it hard to predict toxicity and tailor the drug to improve efficacy. Despite interest in dengue antivirals, no dengue antiviral has successfully passed clinical testing suggesting a need for a better antiviral screening platform that can combine the advantages of in vitro and in vivo assays. We plan to use our proprietary RNA aptamer technology to develop a target-specific cell-based HTS platform targeting the RNA-dependent RNA polymerase (RdRP) of dengue virus. RdRP is an ideal target in Dengue due to its high identity across serotypes, and an ideal target in RNA viruses because of its critical role in viral replication, and its lack of a mammalian counterpart. The goal of this application is to develop a fluorescent sensor capable of monitoring RdRP transcription in a cell line stably expressing viral proteins to advance dengue antiviral discovery. Phase II of this application is to develop a completely comprehensive cell line stably expressing both viral proteins and a fluorescent sensor for use in HTS assays. Phase II will also include the development of similar assays for other viruses, including Zika and Ebola, based off design knowledge from this Phase I grant.
For more information, please reach out at contact@lucernatechnologies.com.
About Lucerna
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.
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