Targeted RNA degradation assay for new antiviral drug discovery
Ended Project Grant Awarded Last action
- Award ID
- R43AI186768
- Recipient
-
Lucerna Inc. UEI J3MWGA6WFCG3
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $300,000
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date
- Originally
- Place of performance
- New York, USA
Award details come from USAspending.gov.
Description
- Abstract
- There are currently no effective vaccines or antiviral drugs for most of the viral diseases afflicting human. Development of new therapy is challenging and expensive, and often complicated by drug resistance. IT is now known that viral transcripts contain many highly structured RNA elements in both the coding and noncoding regions, and they play key roles in the viral life cycle. Many of these elements are highly conserved and, thus, they are attractive new targets that potentially have lower likelihoods of viral resistance development. Targeted RNA degradation (TRD) is an emerging strategy in recent efforts to further discover new antiviral small molecules with privileged scaffolds and better resistance profiles. However, early-stage TRD drug discovery has been hindered by current high-throughput screening (HTS) assay technologies designed for protein targets. Virtually all cell-based drug screens used minigene reporters that rely on luciferase or fluorescent protein signals for assay read-out. Minigene reporter design is straightforward but minigene reporter requires mrna export to the cytosol and protein translation. This significantly increases the rate of false hits per screen since compounds that inhibit global protein translation machinery or RNA export will also impact reporter read-out. Assays that monitor endogenous RNA levels are low-throughput or time-consuming, involve multiple steps, and not readily adaptable for high-throughput SM screening. Thus, there is an unmet need for a new cell-based HTS assay platform that monitors target RNA turnover directly, reflects real-time RNA dynamics, and compatible for different types of RNA and different TRD approaches. For proof-of-concept, this project aims to develop HTS-compatible reporters that can measure drug- induced changes of RNA levels of dengue and influenza viruses, two global pathogens with different genomic structures and life cycles. The ultimate product of this sbir project will be a cell-based HTS assay platform that can accelerate the early-stage discovery of TRD drugs toward previously intractable viral diseases.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Original award | $300,000 |
Quick answers
Who received award R43AI186768?
R43AI186768 was awarded to Lucerna Inc. by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on August 1, 2024.
How much is award R43AI186768 worth?
$300,000 has been obligated on R43AI186768.
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