March 2019

Boston, MA

Day One
Wednesday, June 13th 2018

Day Two
Thursday, June 14th 2018


Chair’s Opening Remarks

CRISPR as a Cure – the Therapeutic Success of CRISPR in Stem Cells & the Potential for More

Using CRISPR/Cas9 to Illuminate Stem Cell Organization & Dynamics

  • Ru Gunawardane Director, Stem Cells and Gene Editing, Allen Institute for Cell Science


• A systematic approach for generating knock-ins in stem cells
• Identifying and improving precision of HDR events
• Use of live imaging and gene editing to explore cell states

When Science Needs The Power Of Story


• Account of self-directed research
• Raising funding and public/press response
• Pathway to recovery
• Patient advocacy tipped the scale for regenerative medicine funding

Eliminating Inherent Genome Editing Bottlenecks in IPSCs to Build Physiologically Relevant Disease Models

  • David Piper Director, Research & Development, Thermo Fisher


• A review of strategies that leverage induced pluripotent stem cells (iPSCs) to increase the relevance of human cell models for in vitro approaches
• Discussion of current advances in genome engineering to pivot from challenges with delivery, identification and selection and subsequent clonal outgrowth by leveraging tools to consistently and reliably generate knock-out and knock-in models for use in target or compound identification
• We demonstrate this approach with iPSCs to build isogenic disease models, which can be further differentiated to various cell types of interest such as cardiomyocytes and dopaminergic neurons to model disease and are more directly related to a disease area than commonly used immortalized cell lines

Speed Networking

Morning Refreshments

Genome Editing B.C.: Lasting Lessons From the “Old Testament”

  • Fyodor Urnov Associate Director, Altius Institute for Biomedical Sciences


• Genome editing with engineered nucleases, a powerful tool for understanding
biological function and revealing causality, was built in a joint effort by academia and
industry in 1994-2010
• Use of CRISPR-Cas9 is the most recent (2013-), and facile, implementation of the
resulting editing toolbox
• Principles and methods of genome editing from the pre-CRISPR era remain relevant
and continue to be useful

CRISPR & Stem Cells: Disease Mechanism & Genome Surgery


• Choosing the right iPSC for the right experiment. The value of isogenic lines
• Building Genome Surgery as field, while developing treatments for specific diseases
• Dominant negative diseases of the retina and motor neurons are early genome surgery targets

Elucidating the Principles of Cancer Cell Immortality Using Genetically Defined Human Stem Cell Models


• Proliferation is required for long-term self-renewal and maintenance of human tissue,
but must be limited to prevent uncontrolled growth associated with tumorigenesis
• TERT is expressed in stem cell compartments, but repressed in most somatic cell types.
In order to understand the regulatory mechanisms of TERT expression in stem cell and
upon differentiation, we study endogenous cis- and trans-elements of the human TERT
promoter in human pluripotent stem cells using genome editing
• We have identified the elements that are required for the expression of TERT in the
stem cell state

Networking lunch

Afternoon Sessions Held at the Allen Institute Back to Basics – Furthering Biological Understanding With the Use of Genetically Manipulated Stem Cells

Meet in the Municipal Room (Exhibit room) for Organized Travel to the Allen Institute

Welcome Presentation from the Allen Institute

  • Rick Horwtiz Executive Director, Allen Institute for Cell Science

Genome & Epigenome Engineering in Organs & Organoids


• Overcoming the special challenges of CRISPR HR in pluripotent stem cells, first published in Jan 2013, has now advanced to full nuclear transfer pig cloning in 2017 for xeno transplantation via apoptosis inhibitors
• We also have a potent path to re-programing stem cells into virtually any set of cell types once we know the RNA profile of the cell targets

Enhancer Switching Regulates Sox2 During the Transition From Embryonic to Neural Stem Cells


• CRISPR-mediated enhancer deletion shows the enhancers required to regulate Sox2 in embryonic and neural stem cells are different
• Chromatin architecture is altered co-incident with the switch in enhancer usage
• Transcription factors bind intergenic regions in ES cells that are poised to regulate Sox2 in neural stem cells

Precise Genome Editing in Human Stem Cells Ex Vivo

Afternoon Refreshments

Modulating RNA Diseases Using CRISPR/Cas Technology

  • Gene Yeo Professor of Cellular & Molecular Medicine, UCSD


  • We are studying RNA diseases such as myotonic dystrophy, huntington’s and ALS.
  • RNA-targeting Cas proteins can modulate and destroy toxic RNA
  • We will present in vivo use of these technologies

Haplotype Editing IPSCs to Demystify Human-Specific & Non-Coding Genomic Disease Risk loci


• Human genetic studies frequently identify risk NSPs or haplotypes in non-coding and human-specific disease risk loci that are not well modeled in rodents
• The 9p21.3 cardiovascular disease risk region is primate specific, contains no coding genes and accounts for ~10-15% of coronary artery disease incidence in the US
• In IPSCs from risk and protected patients we deleted the entire ~60kb haplotype and performed RNA-Seq throughout differentiation of vascular smooth muscle cells – a strongly implicated causative cell type
• Deletion of the risk haplotype specifically rescues VSMC function and identifies new target molecules and pathways relevant to cardiovascular disease

Chair’s Closing Remarks

Drinks & Poster Session Hosted by the Allen Institute for Cell Science