March 2019

Boston, MA

Day One
Wednesday, June 13th 2018

Day Two
Thursday, June 14th 2018

Morning Coffee & Refreshments

Chair’s Opening Remarks

A Continued Discussion of Using CRISPR for Regulating the Genome

Elucidating Disease Mechanisms & Therapeutic Targets in Human IPSC Models by CRISPR-Based Functional Genomics


• We have established genetic screens based on CRISPR, CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) in human iPSC-derived cell types
• Genetic modifier screens in patient-derived iPSCs and isogenic CRISPR-corrected lines can reveal mechanisms of disease-associated genes and therapeutic strategies
• We have established cellular phenotypes relevant for neurodegenerative diseases in human iPSC-derived neurons, astrocytes and microglia and conducted first genetic modifier screens in a pooled format
• We are also establishing a platform for CRISPR-based arrayed high-content screens in iPSC-derived cells to investigate complex and non-cell autonomous phenotypes

Combining Patient-Derived IPSCs & CRISPR Technology in Disease Modeling & Drug Discovery for Rare Genetic Disorders


• “Cluster-and-conquer” approach for >80 rare human diseases linked to the intermediate filament gene family
• CRISPR/Cas9 gene editing of Alexander Disease and Giant Axonal Neuropathy patient iPSCs to obtain isogenic control cells
• 2D and 3D differentiation platforms using disease mutant and isogenic control iPSCs to generate astrocytes and neurons
• Validation of disease targets and testing of small molecule compounds in iPSCsderived astrocytes

Morning Refreshments

A Scaled Framework for CRISPR Editing of Human Pluripotent Stem Cells to Study Psychiatric Disease


• We report a standardized CRISPR-Cas9 approach with robust benchmarking at each step to edit a large set of psychiatric disease-implicated genes in hPSCs
• Transcriptional state and nucleosome positioning around targeted loci are not correlated with CRISPR editing efficiency
• Editing frequencies vary between different hPSC lines and correlate with genomic stability
• Precision editing with small and large ssDNAs provides an efficient platform for future editing frameworks

Synthetic sgRNA Enables Highly Efficient & Consistent CRISPR Editing of Cells for Automation, Cell Engineering & Therapeutic Applications


• Achieving consistent and high editing efficiencies with CRISPR is critical for automation, cell engineering and therapeutic applications with primary cells, and remains a significant challenge
• Through a collaborative effort, we demonstrate that use of synthetic sgRNA for CRISPR yields improved and consistent editing efficiencies that are required for such applications

Gene Repair in Human Hematopoietic Stem Cells

  • Jenny Shin Jacob Corn’s Lab Postdoctoral Researcher, Jacob Corn’s Lab Innovative Genomics Institute UC Berkeley


• Mechanisms of HDR in human cells
• Challenges of editing in hematopoietic stem cells
• Progress towards translation of gene editing therapies for sickle cell disease

Lunch & Networking

Using CRISPR to Illuminate Organs & Organoids


– Kidney organoids derived from Allen Institute iPS cell lines reveal organelle dynamics at the tissue scale

– CRISPR can be used to knock out whole organelles in human tissues

– Using CRISPR in embryos allows the growth of entire organs from a different species in mice

CRISPRing iPSCs to Efficiently Model Genetic Diseases


• Generating iPSC from patients with genetic disorders
• Creating isogenic iPSCs for disease modeling with the CRISPR/Cas9 system
• Applying the CRISPR/Cas9 system to Cerebral Cavernous Malformation (CCM) patientspecific iPSCs to generate knockout models
• Developing 3D culture platforms of iPSCs-derived endothelial cells for transcriptome and proteomic studies

Afternoon Refreshments

Round table sessions


Chair’s Closing Remarks

Close of CRISPR Stem Cell Congress 2018

Human IPSC-Based Disease Modeling Reveals a Retrotransposon With Repeat Expansion as the Causal Mechanism of X-Linked Dystonia Parkinsonism


• Human iPSC-based XDP disease modeling reveals causative mutation of XDP
• An XDP-specific SVA insertion induces intron retention and down-regulation of TAF1
• CRISPR/Cas9 excision of SVA rescues aberrant splicing and cTAF1 expression in XDP
• Expression profiling implicates neurodevelopment and dystonia pathways in XDP iPSCderived neural cells