Discussion Day

Building for Building’s Sake? Delivering CRISPR Apparatus More Effectively

9:00 am Chair’s Opening Remarks

9:15 am Why Isn’t the Future of Medicine Here Yet?

  • Brett Staahl Founder & Head of Applied Technologies , Scribe Therapeutics

Synopsis

  • Genetic Understanding: Gene editing requires knowledge of the underlying genetic causes and what type of edits to make
  • Delivery: We need robust, reliable and safe strategies for delivering genomeediting enzymes to the cells in need of repair
  • Efficacy: Inactivating a disease causing gene can be done reliably, it is currently inefficient to “paste” the corrected gene

Evaluating Potential Delivery Modalities: Mechanical, Viral & Non-Viral Candidates

9:45 am Directed Evolution of Novel AAV Variants for Clinical Gene Therapy

Synopsis

  • Highly efficient, targeted AAV vectors may be needed to fully unlock the potential of gene therapy
  • Directed evolution has proven to be a powerful approach to engineer highly optimized AAV variants
  • We have been implementing this approach to engineer novel AAVs for clinical translation

10:15 am Overcoming Limitations of Viral Vectors to Deliver CRISPR Machinery

Synopsis

  • Exploring current capabilities of viral vectors to deliver genetic materials
  • Discussing CRISPR-specific delivery challenges that affect vector choice
  • Evolving vectors to increase delivery efficiency and specificity

10:45 am Morning Refreshments

11:15 am Gene Editing After Local Injection: Non-Viral Delivery

  • Niren Murthy Professor , University of California at Berkeley

Synopsis

  • Gene editing in the brain after an intracranial injection of the Cas9 RNP complexed to nanoparticles
  • Gene editing in muscle tissue after an intramuscular injection of the Cas9 RNP complexed to nanoparticles
  • New protein conjugation strategies
  • New delivery strategies for the Cas9 RNP

11:45 am Non-Viral Delivery of CRISPR Using Polymer Nanoparticles

  • Kunwoo Lee Chief Executive Officer & Co-Founder , GenEdit

Synopsis

  •  Understanding factors that affect non-viral CRISPR delivery
  • Assessing how systematic screening helps delivery design
  • Demonstration of delivery of mRNA and protein

12:15 pm

  • Kunwoo Lee Chief Executive Officer & Co-Founder , GenEdit
  • Delai Chen Associate Director, Nanoparticle Formulation , Beam Therapeutics

Synopsis

Panel Discussion: Discussing the Future of CRISPR Delivery: Will One Modality Emerge as Superior?
Looking forward to therapeutic CRISPR application means that a high quality, effective, and reliable vector will be required to deliver CRISPR apparatus to cells that need it. This panel discussion will discuss questions surrounding vector choice, including:
• How can non-viral delivery mechanisms become more targeted?
• Will one delivery mechanism be superior against all others?
• Which factors will affect vector choice?
• Are current methods good enough to deliver CRISPR?
• What regulatory requirements surround CRISPR delivery?
• How can potential immune response to CRISPR-Cas be minimized?

12:45 pm Lunch & Networking

Transitioning from Ex Vivo to In Vivo CRISPR Delivery

2:00 pm Improved Non-Viral Vectors for In Vivo Genome Editing

  • Amr Abdeen Postdoctoral Associate, University of Wisconsin- Madison

Synopsis

  • Current challenges facing non-viral vectors for therapeutic use and how to address them
  •  Assessing whether non-viral or viral vectors are more applicable for delivering CRISPR apparatus specifically
  • Developing non-viral vectors to target different cell types ex vivo and in vivo

2:30 pm Delivering CRISPR Apparatus In Vivo Using Nanoparticle Technology

Synopsis

  •  Achieving in vivo CRISPR delivery directly in animals
  • Exploring tissue types that have potential to be targeted successfully in vivo
  • Discussing specificity concerns of in vivo delivery
  • Thousands of nanoparticles can be tested in vivo using DNA barcodes

3:00 pm CellSQZ platform for Development of Next Generation Cell Therapies

Synopsis

  • Microfluidic cell deformation (CellSQZ) is broadly applicable to a variety of primary cell types and cargos
  •  Platform enables multiplex engineering with high viability and delivery
  •  CellSQZ shows reduced potential for cell toxicity and off-target effects seen by other methods
  • Platform is scalable and allows both research and clinical use

3:30 pm Chair’s Closing Remarks

3:45 pm Close of Discussion Day