8:00 am Morning Coffee & Light Breakfast
8:50 am Chair’s Opening Remarks
Highlighting Strategies for Optimizing RNA Editing Therapeutics to Effectively Treat a Wide Landscape of Genetic Diseases
9:00 am Unlocking the Edit-Verse: Combining Machine Learning & Multiple AIMer Applications to Build a High-Impact RNA Editing Pipeline
Synopsis
- Leveraging deep learning models and genetic datasets to identify new RNA editing targets and edit sites
- New opportunities in correction and mRNA upregulation in hepatic and non-hepatic diseases
9:30 am Wobble Base Pairs Enable Site-Directed RNA Base Editing with High Efficiency & Precision in-vivo
Synopsis
- GU wobble base pairs in the context of RNA editing
- In-silico optimized guide RNA design
- Limiting factors for RNA base editing in the murine CNS
10:00 am Morning Break & Networking
Addressing Challenges of Durability to Achieve More Effective Therapeutics for Treating Rare Diseases
11:00 am Roundtable Discussion: Discussing Strategies for Improved Longevity of Editing Therapeutics to Achieve More Durable Effects
Synopsis
- How can the delivery platform used enhance the durability of the RNA editing machinery?
- Is it possible to incorporate self-replicating RNA for continued editing to increase longevity?
- What strategies is the community currently trying to improve durability? Is it possible to incorporate the RNA editing system into the genome?
12:00 pm Lunch & Networking
Uncovering Brand-New Data Updates for Progression Towards the Clinic & Accelerating Development of RNA Editors
1:00 pm RestorAATion: First Clinical Progam Evaluating an RNA Editing Therapeutics in Humans
Synopsis
- Preclinical data supporting WVE-006 as a best-in-class approach for AATD
- Overview of RestorAATion study program
1:30 pm Edit the Message: Rewrite the Future
Synopsis
- At Korro Bio, we are developing our proprietary OPERA platform (Oligonucleotide Promoted Editing of RNA), which utilizes synthetic oligonucleotides that recruit adenosine deaminases acting on RNA (ADARs) to repair disease-causing mutations at the RNA level
- In addition to repairing standard G-to-A mutations, our platform enables the modulation of protein function by changing the amino acid code
- This presentation will provide an update on our OPERA platform and our progress towards the clinic
2:00 pm Developing Axiomer RNA Editing Technology Towards Clinical Development
Synopsis
- Increasing knowledge of ADAR biology, selecting models for prediction of Axiomer potential in human tissue, and ensuring EON sequence and delivery optimization
- Reviewing the potential of Axiomer platform editing capabilities in vivo and assessing functional effect in therapeutic targets
- Developing Axiomer RNA editing platform in preparation for clinical development and supporting discovery of new therapeutic applications
2:30 pm Afternoon Break & Networking
Identifying New Applications of RNA Editing to Unleash its Full Potential for Accelerated Treatment of More Widespread Disease
3:30 pm RADAR: An ADAR-Based Technology for Selective Translation of Therapeutic Proteins
Synopsis
- RADAR enables cell-type specific RNA expression by sensing intracellular RNA markers that define the cell type, disease state or cell state of interest to activate translation of a synthetic transcript
- We are inspired by ADAR biology to promote efficient editing of exogenous mRNA substrates in a marker-dependent manner
- RADAR enables precise, autonomous cell-selectivity that can bring specificity to broadly-targeting delivery vectors for DNA and mRNA
4:00 pm Engineering gRNA-Free Single Enzymes for Programmable RNA Base Editing RNA
Synopsis
- We developed a new system by combining programmable RNA binding domains with different RNA deaminase domains (i.e., functional module), achieving specific and efficient RNA base editing for both A-to-G and C-to-U conversion. All these editing enzymes are originated from human proteins, suggesting a low immunity compared to the CRISPR-based editing systems that contain bacterial proteins
- The RNA deaminase domains (APOBECs) were further modified to optimize the specificity and efficiency of base editing, achieving effective C-to-U editing in all sequence contexts
- This system showed high efficiency to correct disease-causing mutations in animal model, especially show phenotypic reversion in a mouse model of autism
4:30 pm miRNA-Based Logic Circuits Encoded on Self-Amplifying RNA for Highly Specific Cancer Cell Classification
Synopsis
- Therapeutic agents encoded on self-amplifying RNA and delivered in LNPs to cells perform multi-input RNA-based logic circuit functions
- Expression of therapeutic proteins and amplification of the RNA within any given cell is determined by the RNA circuit based on the presence or absence of several RNA biomarkers
- Multiple RNA inputs affect the state and stability of the RNA molecule encoding the therapeutic programs