8:00 am Breakfast & Registration

8:30 am Chair’s Opening Remarks and State of Address


Points to consider throughout the meeting with respect to current affairs surrounding CRISPR:
• Where are we with this technology and have we gone too far? What’s in store for
the future?
• Where do we stand in terms of gene drive, public health and the resulting ethical
considerations of genome editing?
• Ultimately, can we marry scientific ambition with ethical constraint?

Pre-clinical and Clinical Insights from Ground Breaking Therapeutic Companies


Faster than we expected, CRISPR translated to the clinic. Through demanding discussions, CRISPR therapeutics have paved the way but what challenges did these ground-breaking therapeutic companies have to overcome, what slowed them down and how did they settle regulatory fears in pioneering this space? In this session we learn about how CRISPR is working in a clinical setting, pre-clinical validation studies and clinical candidates for CRISPR based cell and gene therapy.

8:40 am CRISPR Therapeutics Provides Clinical Insights into CTX001 for the Treatment of Sickle Cell Disease

  • TJ Cradick Head of Genome Editing, CRISPR Therapeutics


• High percentage of gene editing and no detectable off-target modifications in human primary CD34+ cells
• Clinically relevant pharmocodynamic effect in edited cells
• Similar rates of editing and effects in patient cells
• Progress on Beta-Thalassemia clinical trial

9:10 am How Gene Editing Therapies Can Treat Genetic Neuromuscular Diseases


• Explanation on how Exonics’ novel SingleCut CRISPR gene editing technology works
• How this technology aims to repair the most frequent mutations causing Duchenne muscular dystrophy

9:40 am Next-generation Gene Editing Technology for Allogeneic T Cell Therapeutics


• Next-generation CRISPR-Cas9 technology with enhanced editing specificity
• Development of CB-010 to treat hematological malignancies

10:10 am Morning Refreshments & Speed Networking

Tools for On and Off-target Characterization and Validation


What’s new in the development of the bioinformatics pipeline? How can we precisely predict genome editingoutcomes? The steps involved in elucidating the validity of the desired edit is crucial to progression of the industry. This session aims to decipher where the industry stands with regards to off-target effects and reiterates the importance of researching DNA repair mechanisms in understanding the effects of CRISPR.

11:10 am Fast and Accurate Quantification of On and Off-target CRISPR Genome Editing Outcomes


• A comparative review of the different methodologies for indel identification
• gRNA dependent non-random indel formation
• gRNA design determined indel outcomes
• Fast and quantitative in vitro, ex vivo and in vivo indel profiling

11:40 am Session details to be confirmed. Please check back for speaker and presentation information

12:10 pm Unbiased Detection of CRISPR Off-targets in Vivo Using Discover-Seq

  • Beeke Wienert Postdoctoral Researcher, Innovative Genomics Institute, Conklin & Corn labs, Gladstone Institutes, San Francisco


• ChIP-Seq for DNA repair proteins provides information on CRISPR-Cas cleavage at a molecular level
• We developed this approach into an unbiased method to detect off-targets after CRISPR-Cas9 editing that we termed DISCOVER-Seq
• DISCOVER-Seq is applicable to cultured cells, primary cells and even allows off-target discovery in animal models (during adenoviral editing)
• DISCOVER-Seq gives novel insight into DNA repair dynamics after CRISPR-Cas9 editing

12:40 pm Precision Gene Editing in iPSC-derived Macrophages for Early Drug Discovery


• Generation of a robust cellular platform to generate human macrophages from differentiated induced pluripotent stem cells (iPSCs) for disease modelling and target validation
• Implementation of precision gene editing in both iPSC and iPSC-macrophages by using CRISPR
• Optimization of single cell deposition of iPSCs to increase throughput and automation in cell line generation

1:10 pm Networking Lunch

Novel Technological Developments That Lead to Increased Safety and Specificity of CRISPR


It’s been demonstrated, optimized and proven –what’s the value of researching beyond Cas9? This session focuses on further optimising Cas9, whilst showcasing what other variants we now have available and introducing base editing: the technique that sets to revolutionalize precision gene editing.

2:10 pm Multiplex Editing & Differentiation

  • George M. Church, PhD. Professor of Genetics Department of Genetics, Blavatnik Institute, Harvard Medical School


• An increasing number of applications need multiplex precise mutations
• These include universal allogeneic cell therapies, CAR-T, xenotransplantation, virusresistant recoding
• Alternatives to CRISPR for this include Integrases, Deaminases, HDR and Lambda Red
• Synthetic tissues for therapies or pre-clinical or individualized trials need differentiation of multiplex cell types in a shared medium

2:40 pm Development of Novel Cas9 and Cas12a Mutants: Defining Editing Efficiency and Specificity

  • Garrett Rettig Director of Molecular Genetics Product Development, IDT


• HiFi Cas9 RNP delivery maintains on-target activity and dramatically reduces offtarget editing
• Conversely, novel Cas12a variants markedly increase on-target editing activity while maintaining the minimal off-target profile
• Multi-plexed amplification via rhAmpSeq is used for target enrichment of genomic loci to provide quantitative NGS assessment of insertions/deletions

3:10 pm Engineering CRISPR Enzymes to have Superior Properties

  • Ben Kleinstiver PhD, Principal Investigator Massachusetts General Hospital Instructor, Harvard Medical School


• Inherent properties of CRISPR nucleases can be suboptimal, leading to insufficient activity, specificity, and targeting range
• We have used directed evolution and rational protein engineering strategies to enhance each of these properties
• Our engineered CRISPR-Cas9 and -Cas12a nucleases improve gene, epigenome, andbase editing

3:40 pm Networking Break and Poster Session

4:20 pm Harnessing Novel CRISPR Systems for Genome Engineering and Human Health


• Discovery of new CRISPR systems expands the molecular toolbox
• RNA editing allows for specific and transient modifications to nucleic acid information
• Evolution of new RNA editing enzymes enables new functionality

4:50 pm The NIH Common Fund Somatic Cell Genome Editing (SCGE) Program: Tools for Translation into the Clinic

  • PJ Brooks Program Coordinator, NIH Common Fund Program on Somatic Cell Genome Editing


• Overview and goals of the NIH SCGE program
• What do we do for diseases that could benefit from genome editing but are so rare that there is no plausible business model?
• Thoughts on developing a CRISPR based platform as a solution for those rare diseases that have no business model
• Open discussion to debate the questions posed for rare diseases

5:20 pm Chair’s Closing Remarks

5:30 pm End of Day One