7:50 am Morning Networking Coffee
8:50 am Chair’s Opening Remarks
Deep Diving into Non-Coding RNA-Based Therapeutics Discovery with Computational Tools to Harness Their Full Therapeutic Potential
9:00 am The Limits of Imperfect: What Do We Know About Low-Homology siRNA Off-Targets?
Synopsis
- siRNA therapeutics are rigorously designed and screened to minimize off-target effects; this is done initially in silico by sequence alignment-based approaches, traditionally using relatively high homology thresholds
- Surprisingly, performing unbiased RNAseq experiments reveals that a significant number of DEGs with low-homology alignments may also be regulated. Here we present a global analysis of what these alignments look like and how they may be informed by our understanding of RNAi biology
- This global analysis was validated by a series of experiments designed to probe the limits of these “imperfect” alignments. Taken together, these findings can help inform future in-silico off-target predictions while minimizing the number of false positives
9:30 am Leveraging Computational Algorithms for Optimal RNAi Design
Synopsis
- Highlighting linear-time algorithms RNA folding
- Harnessing design algorithms to fight Covid-19 with RNAi therapeutics
10:00 am Morning Networking Break
11:00 am Unlocking In Vivo AI Driven tRNA Suppressor Evolution at Single Cell Resolution
Synopsis
- Outlining novel in vivo tRNA suppressor reporter mouse models
- Highlighting library design combining generative and predictive LLM models
- Deep mining tRNA suppressor library using single cell RNAseq
11:30 am Roundtable Discussion: Harnessing AI to Optimally Design tRNA for Enhanced tRNA Durability & Delivery
Synopsis
- How can we control tRNA expression, durability and delivery for tRNA therapeutics?
- How can we harness sequence and chemical modifications for tRNA design?
- Leveraging learnings from siRNA therapeutic design and delivery with computational tools
12:30 pm Networking Lunch
RNA Programming & Logic Gates: The Future of Smart Computation to Unlock CellResponsive & Real-Time Expression RNA Therapeutics
1:30 pm Exploring & Understanding Programmable RNA Therapeutics to Unlock a New Wave of Cellular Control Mechanisms
Synopsis
- Outlining the concept of RNA programming and logic gates to regulate protein expression or gene expression in a cell
- Revealing successes and future applications of RNA logic gates for logic computation in mammalian cells
- Extracting key factors and setbacks that are hindering the successful implementation of RNA reprogramming technologies into the clinic
2:00 pm Mastermind Discussion: Controlling the System: Leveraging Computational Tools to Control the Level of Expression for mRNA and RNAi Programmable Therapeutics to Develop ‘Smart RNA’
Synopsis
- How can computational tools be utilized in the development of mRNA & RNAi programmable therapeutics?
- What is the potential for leveraging ‘smart RNA’ to optimize dosage, timing and minimizing off-target effects?
2:30 pm Leveraging AI & RNA Technology to Design Programmable RNA Medicines
Synopsis
- Harnessing high throughput screening to enable accurate modeling of ADAR-mediated RNA editing in vitro
- Utilizing generative modeling to allow de novo guide RNA designs for RNA editing
- Spotlighting transfer learning to leverage smaller datasets to optimize guide RNA designs for in cell performance