*Please note that all agenda timings are Eastern Time. For PDT time,

(please download the full program here.)

8:00 am Online Networking

Synopsis

Grab a quick cup of tea or coffee from the comfort of your own home office and jump straight into your opportunity to connect with new contacts from active companies in the field and exchange digital business cards. Network and form lasting connections through this exclusive virtual speed networking!

8:50 am Chair’s Opening Remarks

Current Strategies for Site-Directed RNA Editing

9:00 am Engineering Therapeutic ADAR Editing Guide RNAs with Maximal Activity & Specificity

  • Adrian Briggs Head of Technology Development, Shape Therapeutics

Synopsis

• Details coming soon

9:30 am C-to-U RNA Editing by APOBEC3A & APOBEC3G Cytidine Deaminases

  • Bora Baysal Professor - Anatomic Pathology, Roswell Park

Synopsis

• Overview of mammalian cytidine deaminases
• Molecular aspects of RNA editing by APOBEC3A in monocytes and macrophages
• RNA editing function of the double-domain anti-HIV cytidine deaminase APOBEC3G

10:00 am What We Can Learn from the RNA Editing of the SARS-CoV-2 Transcriptome

Synopsis

• SARS-CoV-2 is actively edited by the host deaminases
• Viral RNA editing provides a catalogue of potential mutations that could be exploited against the virus
• The analysis of the RNA editing points towards the specificities of APOBEC targeting

10:30 am Online Virtual Networking Break

Synopsis

Grab a quick cup of tea or coffee from the comfort of your own home office and jump straight into your opportunity to connect with new contacts from active companies in the field and exchange digital business cards. Network and form lasting connections through this exclusive virtual speed networking!

11:30 am Cas & Non-Cas Proteins for RNA Modulation: RNA Editing & Beyond

Synopsis

• Overview of naturally-occurring Cas proteins, as well as synthetic, non- Cas proteins engineered to target and modulate RNA transcripts
• Expand on RNA binding proteins and effector domains designed to target disease-causing RNA, with a particular focus on the following therapeutic modalities: destroying dysfunctional RNA, destroying dysfunctional RNA and replacing it with a normal copy, enhancing RNA translation to produce more of a specific protein, modifying splicing, and RNA editing
• Explore the therapeutic applications of the versatile RNA targeting and RNA modification mechanisms in addressing neuromuscular, neurodegenerative and ophthalmological diseases

12:15 pm Panel Discussion: Chemical Modifications of RNA

Synopsis

• Are there RNA chemistry except we’re not addressing or are there RNA chemistry more optimal than others?
• Discussing informatic based approaches to understanding RNA editing, to the biochemistry around it to application
• What components go into a drug molecule to ensure that you’re getting the right response from a pharmacological perspective of the edit?
• Exploring synthetic chemistry approaches

1:00 pm Online Networking Lunch

Synopsis

Grab a bite to eat from the comfort of your own home office and continue the virtual networking to connect with new contacts from active companies in the field and exchange digital business cards. Network and form lasting connections through this exclusive virtual speed networking!

Mitigating Against Off-Target Editing

2:00 pm Global Quantification Exposes Most DNA & RNA Off-Target Activity by Base Editors is Non-Specific

Synopsis

• Off-target edits are a major concern limiting the application of base editors. Multiple studies have been dedicated to identification of these events and further enzyme optimization to suppress them
• These studies have mainly focused on strongly edited off-target sites, where editing affects an appreciable fraction (>10%) of transcripts. We point out that the majority of off-target activity of the deaminases is nonspecific, seemingly stochastic, and deaminates a large number of sites throughout the genome or the transcriptome, at a low editing probability per site per molecule
• Here we employ a complementary computational approach that is sensitive to the stochastic off-targets activity, and show that off-target RNA and DNA mutations are abundant even for current optimized deaminase editors. We provide a computational tool to quantify global off-target activity, which can be used to optimize future base editors

Sequence Design of Guide RNAs

2:30 pm Harnessing Endogenous ADAR

Synopsis

• Demonstrating guideRNA design
• Reviewing ASO design

3:00 pm Afternoon Online Networking Break

Synopsis

Grab a quick cup of tea or coffee from the comfort of your own home office and jump straight into your opportunity to connect with new contacts from active companies in the field and exchange digital business cards. Network and form lasting connections through this exclusive virtual speed networking!

3:30 pm Round Table Discussions:

Ensuring Safety & Stability Whilst Maintaining Efficiency
• Can we predict what modifications will be toxic?
• Can you use a small molecule to take out the form of ADAR enzyme that tumor depends upon to lower the risk of toxicity to normal cells?
• How can we ultimately deliver safe and effective transcriptome edits?
• What are the clinical safety concerns with editing?

Sequence Design of Guide RNAs
• How damaging is our guide RNA when it binds to non-specific position?
• What is the potential of engineered RNA editing-guided technique in treating hypo-editedrelated diseases?
• Redirecting endogenous ADAR to new sites by making editable structures using antisense RNA oligonucleotides
• Do complexes between ADAR and antisense RNAs recycle to hit more than one mRNA?

What is the Longevity of Response?
• How long will the therapy remain in the tissue/cell, and what is the dosing considerations?
• What is the significance of A-to-I RNA editing of transcripts modulating pharmacokinetics and pharmacodynamics
• Modifying RNA to make it less biodegradable while still functional

5:00 pm Chair’s Closing Remarks & End of Day One