8:00 am Coffee & Registration

8:30 am Chair’s Opening Remarks

Synopsis

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

UNCOVERING HOW RNA ACTUALLY FUNCTIONS & EXPLORING THE EMERGING & DIFFERENT APPROACHES FOR DIRECTED RNA EDITING

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

Synopsis

• 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

Synopsis

• 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

Synopsis

• 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

Synopsis

• 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

Synopsis

• 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

Synopsis

• 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

Synopsis

• 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

Synopsis

– 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?

Synopsis

• 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

Synopsis

– 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

Synopsis

• 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