Explore the Agenda
8:30 am Check In & Light Breakfast
8:50 am Chair’s Opening Remarks
Optimizing Editing Efficiency by Designing Durable Guide RNA & Effectively Recruiting Editing Machinery to Target Sites to Increase Magnitude of Modification
9:00 am Harnessing Endogenous ADAR for Oligo-Directed RNA Editing
• The OPERA platform (Oligonucleotide Promoted Editing of RNA), which utilizes synthetic oligonucleotides that recruit 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
• Updates on the OPERA platform and progress towards the clinic
9:30 am Advancing ADAR Mediated RNA Editing Therapies: An Optimal Platform for Treatment of Rare & Common Genetic Diseases
- Platform Innovation: RESTORE+ platform leverages proprietary GalNAc delivery and enhanced chemistry to maximize RNA editing potency, durability, and safety
- Targeted Liver Delivery: Engineered for precise ADAR-mediated editing with minimized safety risks, ensuring effective hepatic targeting
- Lead Program in AATD: Focused on addressing the genetic root of Alpha-1 Antitrypsin Deficiency to offer a transformative therapeutic option
10:00 am Morning Break & Speed Networking
This is your opportunity to connect and establish meaningful industry relationships with some of the biggest names in RNA editing!
Unleashing the Full Therapeutic Impact of RNA Editing Through Deep Understanding of RNA Structure & ADAR to Ensure Efficacious Editing
11:00 am Molecular Basis of ADAR1-Mediated RNA Editing
• Outlining the biochemical profiling of ADAR1’s RNA substrate preference
• Comprehending atomic resolution structures of ADAR1
• Understanding the domain requirement for RNA editing
11:30 am Structure-Guided Optimization of ADAR-Guiding Oligonucleotides
• High resolution structures of ADAR-RNA complexes solved by X-ray crystallography and cryo-EM
• Describing the impact of specific nucleoside analogs at different positions in ADAR guide strands
• Shedding light on the mechanism of the ADAR deamination reaction and informing the design of highly efficient and selective ADAR guide strand for therapeutic editing using chemically modified RNA
12:00 pm Lunch Break & Networking
Exploring Novel Editing Technologies Beyond ADAR to Increase the Scope of RNA Modification & Reach Previously Undruggable Patient Populations
1:00 pm Programmable Multi-Kilobase RNA Editing with Splice Editors
• Amber Bio is building Splice Editors, a novel RNA editing technology
• Exploring the ways Splice Editors can achieve multi-kilobase edits with a single AAV
• Understanding how Splice Editors open the aperture for addressable targets
1:30 pm Break-and-Repair RNA Editing with CRISPR Ribonucleases
• Sequence-specific RNA cleavage by CRISPR ribonucleases and subsequent RNA repair enables programmable RNA editing
• Break-and-repair RNA editing facilitates engineering of RNA viruses without DNA intermediate
• CRISPR-guided RNA breaks are repaired in human cells, which can be used for programmable RNA excisions to restore gene function
2:00 pm High Fidelity RNA Editor Development & Studies Supporting the World’s First CRISPR/RNA-Targeting Therapy, HG202, for Patients with Neovascular Age-Related Macular Degeneration
- Identification, protein engineering and characterization of high fidelity hfCas12Y
- The opportunity and advantages or RNA editing for Neovascular Age-Related Macular Degeneration (nAMD)
- The molecular composition, mechanism of action, and preclinical animal studies of RNA editor HG202
2:30 pm Programmable RNA Writing with Trans-Splicing
- Utilizing trans-splicing technology to replace large RNA segments, enabling the correction of multiple mutations at once
- Demonstrated correction for transcripts of therapeutically relevant genes, including those implicated in Huntington's Disease and Rett Syndrome
- Protein-free system design allows for efficient AAV delivery, facilitating in vivo RNA correction strategies
3:00 pm Afternoon Break & Poster Session
Please visit the website for T&Cs of submitting a poster.
Promoting Specific Targeting & Enhanced RNA Delivery to Extra-Hepatic Targets to Maximize Bioavailability & Reach the Therapeutic Potential of RNA Editing
4:00 pm Round Table Discussion: Limiting Off-Target Effects by Ensuring Specific Payload Delivery with Highly-Specific Guide RNA to Prioritize Patient Safety
• Utilizing transcriptomic data to assess peripheral sequences and empirically monitor off-target edits
• Designing guide RNA for maximum durability and specificity to limit toxicity and immunogenicity
• Determining safety thresholds and acceptable levels of off-target editing
4:45 pm RNAfix Drives Efficient RNA Editing in the Non-Human Primate CNS with IV Delivery
• RNAfix uses ADAR-recruiting guide RNAs to achieve >90% in vivo A-to-I editing efficiency in mouse and NHP CNS with exquisite transcriptome-wide specificity
• Shape’s novel AAV capsid SHP-DB1 efficiently crosses the NHP blood-brain-barrier following IV administration, delivering RNA editing across the entire brain without invasive cranial injections
• ShapeTX’s integrated platform combines AI-optimized RNAfix guide RNAs, proprietary CNS-tropic AAV capsids, and disruptive stable cell line AAV manufacturing to overcome key gene therapy limitations, enabling scalable, cost-effective solutions to address unmet needs in neurological disorders
