8:00 am Coffee & Registration

8:30 am Chair’s Opening Remarks


Overview as to why RNA Editing is presently reaching an inflection point and the applications that the industry believes RNA Editing could tackle.


8:40 am Directed RNA Editing, How it has Evolved and General Applications


• Limitations of the systems and how to get beyond these
• New enzymatic functions and how to discover more
• If we can determine C-U editing, we can double the applications
• Considerations of longevity of response to tailor for transient and temporary conditions (setting ourselves apart from CRISPR cas 9)
• Speculation about the future and where the various systems might be heading

9:10 am RNA Editing with CRISPR-based systems


• Introducing RNA editing for programmable A to I (G) replacement (REPAIR)
• Designing and building a robust RNA editor
• Directed evolution of ADAR2 to enable RNA Editing for Specific C to U Exchange (RESCUE)
• Applications of REPAIR and RESCUE

9:50 am Current Strategies for Site-Directed RNA editing using ADARs


• Discuss the different SDRE strategies that have been developed in order to correct G to A genetic mutations and engineer protein function
• Difference and comparisons between approaches:
• First approach coupling the catalytic domain of ADAR to a guide RNA and a second approach mimicking naturally occurring RNA structures to recruit endogenous ADAR to specific target mRNAs.
• Challenges to overcome

10:20am Morning Refreshments & Networking Break

11:20 am Developing Technology & Algorithms to Uncover A-to-I RNA Editing in Humans & Animal Models


• RNA editing can be found directly from sequencing data
• Algorithms to detect editing events and to distinguish them from mutations and errors are presented
• Systematic mapping of the editome across the animal kingdom has revealed that most A-to-I editing sites are located within mobile elements
• Both recoding and non-coding events have implications for genome evolution and, when deregulated, may lead to disease

11:50 am RNA Editing: Engineering editases, guideRNAs, and ASOs for application in Life Sciences and Medicine


• Engineering editing systems (concept and properties of SNAP-ADARs)
• Harnessing endogenous ADARs with chemically stabilized ASOs
• Harnessing endogenous ADARs with encodable guideRNAs

12:20 pm Targeting RNA modifying enzymes for the treatment of cancer


• Targeting RNA pathways via RNA modifying enzymes
• Learnings from Methyltransferases – druggability, efficacy and safety
• Overcoming a key challenge in the field: quantitative analysis of RNA modifications using mass spec and other approaches
• Perspectives on RNA editing

12:40pm Networking Lunch

1:50 pm Identification and modulation of RNA binding protein binding sites

  • Gene Yeo Professor, University of California, San Diego


• Systematic comparisons of A-to-I modulation by CRISPR/Cas formulations
• RNA editing to mark RNA binding protein-RNA interaction sites

2:20 pm Recruitment of Endogenous and Exogenous ADARs for RNA Editing New Approaches and New Challenges

  • Prashant Mali Assistant Professor, Bioengineering, University of San Diego


– Genetically encodable RNA Editing platforms
– Engineering activity & specificity
– In vivo RNA editing

2:50 pm Panel Discussion: RNA Off-Target Effects, How Detrimental Are They?


• Defining the difference between genomic off targets and RNA off-targets
• What level of off targets are permissible? How do we determine this?
• Validation that RNA off-target effects are not detrimental
• How damaging is our guide RNA when it binds to non-specific positions

2:40pm Afternoon Break & Poster Session

3:50 pm Cellular impact of the RNA modification machinery on pre-mRNA splicing, ribosome biogenesis, and telomere length regulation


– Subcellular localization of RNPs matters for RNA modification efficiency
– 2’-O-methylation of snRNAs is important for pre-mRNA splicing
– Cajal body localization of the telomerase RNP is important for telomere length regulation
– Nopp140 is the underlying principle for Cajal body localization

4:20 pm Suppression of nonsense mutations in disease genes by targeted RNA pseudouridylation

  • Yi-Tao Yu Principal Investigator and Professor, University of Rochester Medical Centre


• Pseudouridylation, which can be catalyzed by RNA-guided mechanism, is the most abundant modification found in RNAs
• By changing the guide sequences within the guide RNA, we can re-direct pseudouridylation to new sites in different types of RNA (e.g., the stop codons within mRNA)
• Pseudouridylation can profoundly alter the chemical properties of an RNA, thus influencing the contributions of the RNA to cellular process in which it participates
• Pseudouridylation at the stop codons can suppress NMD and promote the translation readthrough of nonsense-containing transcripts, thus offering an opportunity to develop a new therapeutic approach to diseases caused by nonsense mutations

4:50 pm Chairs Closing Remarks

5:00 pm End of Day One of 1st RNA Editing Summit 2019