CONFERENCE DAY TWO

8:30 am Morning Coffee & Light Breakfast

8:50 am Chair’s Opening Remarks

Improving RNA Splicing Modulation through Assay & Screening Strategies for Identifying more Effective, Selective & Potent Small Molecules

9:00 am Development of Biophysical Assays to Explore MOA of HTT Splicing Modulation by SM

Synopsis

  • Development of MST and SPR assays to measure SM binding to HTT RNA
  • SM-RNA Chair’s epitope mapping by NMR
  • Development of biophysical assays to measure SM-mediated U1snRNP association

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9:30 am Selectivity Profiling of RNA Splicing Modulators to Understand Efficacy & Off-Target Effects

Synopsis

  • Progress toward a comprehensive understanding of selectivity as applied to small molecule splicing modulators
  • Transcriptomic analysis of differential gene expression and splicing events
  • Delineating relationships between activity, selectivity, and structure

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10:00 am Morning Break & Networking

Leveraging RNA Assays to Realize the True Mechanism of Action of RNA-Targeting Small Molecules to Validate Therapeutic Effect

11:00 am Panel Discussion – Revolutionizing RNA Assays to Characterize the Mechanism of Action for Advancing RNA Targeted Drug Development

  • Anant Agrawal Director, RNA Platform & Target Enablement, Remix Therapeutics
  • Linlong Xue Associate Scientific Director, Biogen

Synopsis

  • Comparing different assay and screening approaches which the field is currently using to better understand the mechanism of action
  • How to optimize current assays to better understand the mechanism of action?
  • How to utilize phenotypic methods to delve into the underlying mechanism?

12:00 pm Lunch & Networking

Uncovering Innovative Assays & Screens for Understanding the Potential of RNA Binding Proteins to Expand the Landscape of Treatable Targets

1:00 pm Chemical Proteomic Methods for Quantifying Protein-RNA Interactions in Cells

Synopsis

  • Chemical proteomics can screen RNA-binding protein (RBP) composition and function in cells using a small molecule probe for rapid gel- and high-content-based detection
  • Chemical proteomics can detect RNA binding activity on known and non-canonical RNA-binding domains with amino acid resolution
  • RBP chemical proteomics offers a screening approach to determine protein off-target activity for RNA binding small molecules

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1:30 pm Assay Technologies to Characterize RNA Binding Proteins & Their Interaction with Target RNA

Synopsis

Details to be revealed

2:00 pm Afternoon Break & Networking

3:00 pm Drug Discovery Efforts on RNA Modifying Proteins

  • Simina Grigoriu Associate Director - Protein & Structural Sciences, Accent Therapeutics

Synopsis

  • Modulation of RNA biology can be driven by inhibition of the proteins that use RNA as a substrate for enzymatic reactions, known as RNA modifying proteins (RMPs)
  • RMPs represent a large class of novel targets for oncology and other disease indications that can be targeted with small molecule inhibitors
  • Accent has developed potent and selective small molecule inhibitors for RMPs across protein target classes, including helicases, deaminases, nucleases and methyltransferases

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3:30 pm Next-Generation Transcriptomic Strategy to Exploit Chemical Biology in RNA Regulator Targeting

  • Nadav Wallis Postdoctoral Researcher – Yeo Lab, University of California San Diego

Synopsis

  • Utilizing transcriptome-wide methodologies, such as STAMP/eCLIP, commonly employed for identifying RNA-binding protein (RBP) binding sites, to profile RBP-RNA interactions within cells upon perturbation by small molecules
  • Profiling small molecule libraries rapidly against RBPs enables the swift generation of comprehensive cellular datasets highlighting the selectivity against RNA targets and other RBPs
  • Leveraging these binding profiles offers an avenue to gain deeper insights into the functional role of targeted RBPs in disease contexts

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4:00 pm Chair’s Closing Remarks

4:30 pm End of the 2nd RNA Assay Development & Screening Summit