American Society of Hematology

2016 Program Schedule for the ASH® Workshop on Genome Editing

Thursday, July 14

8:00 a.m. - 8:30 a.m.Breakfast
8:30 a.m. - 8:45 a.m.Welcome, Introductions, and Announcements
Mitchell Weiss, MD, PhD
St. Jude Children’s Research
Hospital Memphis, TN
Program Co-Chair

J. Keith Joung, MD, PhD
Massachusetts General Hospital and Harvard Medical School
Boston, MA
Program Co-Chair

Philip Gregory, D.Phil
bluebird bio, Inc.
Cambridge, MA
Program Co-Chair
8:45 a.m.- 9:30 a.m.Keynote address: Manipulating the Genome for Research and Therapy
Stuart Orkin, MD
Dana-Farber Cancer Institute, Children’s Hospital
Boston, MA

Dr. Orkin will provide a general background on the applications of genome manipulation and editing in hematology research and discuss specific examples that highlight recent advances. The goal of this talk will be to describe how genome manipulation is revolutionizing diverse aspects of research relevant to hematology and may shape future therapies.
9:30 a.m. - 10:30 a.m.Session 1: Emerging Advances in Genome Editing Technologies
Chair:
J. Keith Joung, MD, PhD
Massachusetts General Hospital and Harvard Medical School
Boston, MA

Genome-editing nucleases have brought powerful new capabilities to biomedical researchers and show promise as potential therapeutic platforms for treating gene-based diseases. Although much progress has been made with these technologies in the past decade, important and innovative improvements to these nuclease platforms continue to emerge at a rapid pace. In this session, speakers will discuss the latest advances in genome-editing nuclease technologies and their application to development of therapeutic strategies for human disease.
9:30 a.m. - 9:50 a.m.Defining and Optimizing the Genome-wide Specificities of CRISPR-Cas Nucleases
J. Keith Joung, MD, PhD
Massachusetts General Hospital and Harvard Medical School
Boston, MA

Dr. Joung will discuss state-of-the-art technologies for defining and improving the genome-wide specificities of CRISPR-Cas nucleases.
9:50 a.m. - 10:10 a.m.Applying gene editing for generating allogeneic CAR T-cells with improved functionalities
Philippe Duchateau, PhD
Cellectis
Paris, France

Dr. Duchateau will present data on the use of TALENs to generate allogeneic CAR-T cells for cancer immunotherapy.
10:10 a.m. - 10:30 a.m.A Tale of Two Specificities: Measuring Cas9 activity and DNA repair outcomes
Andrew May, DPhil
Caribou Biosciences
Berkley, CA

Dr. May will describe novel methods for assessing on- and off-target effects of CRISPR-Cas nucleases and the implications for their design and assessment.
10:30 a.m. - 11:00 a.m.Panel Discussion
11:00 a.m. - 11:15 a.m.Break
11:15 a.m. - 12:15 p.m.Session 2: Emerging Advances in Genome Editing Technologies (Continued)
Chair:
J. Keith Joung, MD, PhD
Massachusetts General Hospital and Harvard Medical School
Boston, MA
11:15 a.m. - 11:35 a.m.Expanding the Versatility of Designed Zinc Finger Nucleases for Genome Editing
Edward Rebar, PhD
Sangamo Biosciences Inc.
Richmond, CA

Dr. Rebar will discuss the design and application of new zinc finger nuclease (ZFN) architectures that increase the targeting range of this platform.
11:35 a.m. - 11:55 a.m.Forcing Enhancer-Promoter Contacts to Understand Enhancer Biology
Gerd Blobel MD, PhD
Children’s Hospital of Philadelphia
Philadelphia, PA

Dr. Blobel will describe methods to induce enhancer-promoter interactions to alter gene expression in human cells using customized site-specific DNA-binding proteins.
11:55 a.m. - 12:15 p.m.A New Approach to Genome Editing
David Liu, PhD
Harvard University
Cambridge, MA

Dr. Liu will present an innovative approach for creating specific DNA sequence changes known as targeted base editing that does not require the use of nucleases or homologous donor templates.
12:15 p.m. - 12:45 p.m.Panel Discussion
12:45 p.m. - 1:30 p.m.Lunch
1:30 p.m. - 2:30 p.m.Session 3: Genome Editing of Stem Cells for Modeling Human Diseases
Chair:
Stuart Orkin, MD
Dana-Farber Cancer Institute, Children’s Hospital
Boston, MA

Somatic cells can be reprogrammed with transcription factors to induced pluripotent stem (iPS) cells, which can be differentiated in vitro into all cell lineages. When derived from patients with genetic disease, iPS cells are thus an invaluable resource for investigating molecular and cellular mechanisms of disease, and for configuring genetic and chemical screens to reverse disease phenotypes. Reverting disease-associated mutations in iPS cells is essential to confirming correlations between genotype and phenotype, and represents a powerful strategy for combining gene and cell therapy. However, classical methods that depend upon endogenous cellular DNA repair pathways for homologous recombination are labor-intensive and inefficient. Recently, several forms of programmable sequence-directed nucleases have been developed that greatly enhance methods of gene repair, providing a powerful toolkit for research and offering considerable therapeutic potential. This session’s speakers will demonstrate how nuclease-mediated gene editing using Zinc Finger Nucleases (ZFNs), TALENs and the CRISPR/Cas9 system can be exploited to model diseases of the hematopoietic and cardiovascular systems.
1:30 p.m. - 1:50 p.m.Genome Editing of Human iPSCs for Modeling Myeloid Transformation
Eirini Papapetrou, MD, PhD
The Mount Sinai Hospital
New York, NY

Dr. Papapetrou will review how ZFNs and iPS cells can be employed to model myeloid disorders.
1:50 p.m. - 2:10 p.m.Development of Efficient Genome Targeting for Correction of Chronic Granulomatous Disease in iPS Cells and CD34+ Hematopoietic Stem Cells
Harry Malech, MD
The National Institute of Allergy and Infectious Diseases
Bethesda, MD

Dr. Malech will present efforts to direct TALENs and CRISPR/Cas9 to revert mutations associated with chronic granulomatous disease.
2:10 p.m. - 2:30 p.m.Genome Editing to Model Cardiovascular Diseases
Kiran Musunuru, MD, PhD, MPH
Harvard University, Brigham and Women's Hospital, The Broad Institute
Boston, MA

Dr. Musunuru will recount how genome editing of iPS cells coupled to differentiation into disease relevant cell lineages can be used to model a variety of cardiovascular diseases.
2:30 p.m. - 3:00 p.m.Panel Discussion
3:00 p.m. - 3:15 p.m.Break
3:15 p.m. - 4:15 p.m.Session 4: Therapeutic Genome Editing for Immune Diseases
Chair:
Andrew Scharenberg, MD
Seattle Children’s Hospital
Seattle, WA

Several groups have recently demonstrated laboratory processes for carrying out efficient genome editing of human primary hematopoietic stem cells and T-cells. Three of the leading investigators in the field will review their respective laboratories progress in moving these advances from the laboratory towards the clinic.
3:15 p.m. - 3:35 p.m.Gene Editing of HSC for the Therapy of Inherited Diseases
Luigi Naldini, MD, PhD
San Raffaele Telethon Institute for Gene Therapy
Milan, Italy

Dr. Naldini will review progress that his laboratory is making in the development of an autologous gene edited hematopoietic stem cell therapy for X-linked severe combined immunodeficiency.
3:35 p.m. - 3:55 p.m.Genome Editing for HIV, A most Unwelcome Genetic Guest
Paula Cannon, PhD
University of Southern California
Los Angeles, CA

Dr. Cannon will discuss her laboratory’s application of nuclease technology for both gene disruption and homology-directed editing of the CCR5 locus in hematopoietic stem cells as a novel approach to therapy of HIV infections.
3:55 p.m. - 4:15 p.m.The "ins" and "outs" of Genetic Engineering of T cells for Human Applications
Laurence Cooper, MD, PhD
ZIOPHARM Oncology, Inc.
Boston, MA

Dr. Cooper will discuss how the combination of gene addition and gene editing can be used to endow human primary T-cells with new properties to enhance their specificity and potency as components of next generation adoptive cellular immunotherapies for cancer.
4:15 p.m. - 4:45 p.m.Panel Discussion
5:00 p.m.Adjourn
5:15 p.m. - 6:15 p.m.Welcome Reception
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Friday, July 15

8:00 a.m. - 9:00 a.m.Breakfast
9:00 a.m. - 10:00 a.m.Session 5: Therapeutic Genome Editing for Hemoglobinopathies
Chair:
Mitchell Weiss, MD, PhD
St. Jude Children’s Research
Hospital Memphis, TN

Sickle cell anemia and beta thalassemia cause major morbidities and mortality in millions of individuals worldwide. These disorders result from inherited mutations in the beta globin gene and represent exciting targets for genome editing therapy via two different strategies. First, non-homologous end joining (NHEJ) may be used to disrupt genomic regions that promote postnatal gamma-to-beta globin gene switching. Consequently, induced gamma globin substitutes for beta globin that is either deficient or defective in beta thalassemia or sickle cell anemia, respectively. Second, homology-directed DNA repair (HDR) may be used to correct some hemoglobinopathy mutations, including the amino acid missense mutation responsible for sickle cell anemia. Both strategies require ex vivo gene editing of autologous hematopoietic stem cells followed by re-infusion into the patient who has received myelo-suppressive or –ablative conditioning. Current challenges include: 1) identifying and minimizing clinically significant off target effects; 2) optimizing the efficiency of gene editing (particularly HDR) in HSCs; and 3) determining appropriate pre-transplant conditioning regimens.
9:00 a.m.- 9:20 a.m.Editing the Genome to Reinstate Fetal Hemoglobin Expression
Daniel Bauer, MD, PhD
Boston Children’s Hospital
Boston, MA

Dr. Bauer will show how CRISPR-Cas9 technology is being used to better understand the mechanisms of BCL11A gene expression and identify new DNA targets for genome editing-mediated induction of gamma globin.
9:20 a.m. - 9:40 a.m.Correction of the Sickle Cell Disease Mutation in Hematopoietic Stem Cells
Zulema Romero Garcia, PhD
University of California Los Angeles
Los Angeles, CA

Dr. Romero Garcia will discuss preclinical studies to correct the sickle cell disease mutation by gene editing-mediated HDR.
9:40 a.m. - 10:00 a.m.Modified Cas9 Ribonucleoprotein/Single Stranded Oligodeoxynucleotide Correction for Sickle Cell Disease
Tim Townes, PhD
University of Alabama at Birmingham
Birmingham, AL

Dr. Townes will describe the development of nine modified Cas9 proteins that can be complexed with a single guide RNA (sgRNA) and a single stranded oligodeoxynucleotide (ssODN) correction template, nucleoporated into primary sickle patient or humanized sickle mouse hematopoietic stem cells and efficiently correct the sickle mutation.
10:00 a.m. - 10:30 a.m.Panel Discussion
10:30 a.m. - 10:45 a.m.Break
10:45 a.m. - 11:45 a.m.Session 6: Advancing Therapeutic Applications of CRISPR-Cas9
Chair:
Philip Gregory, D.Phil
bluebird bio, Inc.
Cambridge, MA

Rapid technological advances in the delivery, activity and specificity of the different genome editing tools are helping to accelerate their development toward potential therapeutic application. Interestingly much of this effort is now being pursued within the biotechnology industry. This session will focus on state-of-the-art genome editing and its applications being developed in some of the genome editing focused companies in the space.
10:45 a.m. - 11:05 a.m.Advancing CRISPR Medicines: Challenges and Solutions
David Bumcrot, PhD
Editas Medicine
Cambridge MA

Dr. Bumcrot from Editas Medicine will discuss potential solutions to the delivery challenges inherent to ex vivo and in vivo applications as well as their approach to evaluating the specificity of Cas9-mediated gene editing.
11:05 a.m. - 11:25 a.m.Bringing CRISPR Therapeutics Into the Clinic
Bill Lundberg, MD
CRISPR Therapeutics
Cambridge, MA

Dr. Lundberg from CRISPR Therapeutics will discuss a number of specific consideration critical to bringing CRISPR/Cas9 technology into clinical stage testing with the goal of developing new, transformative therapies for patients with serious diseases.
11:25 a.m. - 11:45 a.m.Gene Editing with megaTALs: Advantages, Challenges, and Future Prospects
Jordan Jarjour, PhD
bluebird bio-Seattle
Seattle, WA

Dr. Jarjour from bluebird bio will discuss the advances made in the development of the megaTAL platform and provide examples of the genome editing outcomes that can be achieved using this system.
11:45 a.m. - 12:15 p.m.Panel Discussion
12:15 p.m. - 1:00 p.m.Lunch
1:00 p.m. - 2:30 p.m.Session 7: Regulatory Issues for Clinical Translation of Genome Editing
Chair:
Paula Cannon, PhD
University of Southern California
Los Angeles, CA

Gene and cell based therapies are subject to review by a number of regulatory bodies, both local and national. Despite the promise of greater precision when compared to standard gene therapy approaches, the newness of genome editing technologies means that the path to approval is currently quite complex. In particular, off target disruptions and potential associated toxicities are a major concern for reviewers. This session will focus on lessons learned from the limited clinical experience to date, and the best practices that are emerging to guide the development of clinical applications.
1:00 p.m. - 1:20 p.m.Regulatory Considerations for Gene Therapy Products involving Gene Editing Technologies
Denise Gavin, PhD
Center for Biologics Evaluation and Research – Food and Drug Administration
Silver Spring, MD

Dr. Gavin will outline the regulatory considerations for when a genome engineering trial is reviewed by the FDA.
1:20 p.m. - 1:50 p.m.Gene Editing Using ZFN Ex Vivo and In Vivo, Pre-Clinical Studies and Clinical Trials
Dale Ando, MD
Sangamo Biosciences Inc.
Richmond, CA

Dr. Ando will describe the experience of Sangamo BioSciences as they developed the first-in-man clinical trial of genome editing, and more recent therapeutic applications.
1:50 p.m. - 2:10 p.m.Translating to Therapy: Moving from the Laboratory to the Patient
Bambi Grilley, RPh, RAC, CIP, CCRC, CCRP
Texas Children's Cancer and Hematology Centers
Houston, TX

Ms. Grilley will discuss the regulatory process and logistics involved in moving a genome editing protocol into the clinic.
2:10 p.m. - 2:30 p.m.Panel Discussion
2:30 p.m. - 3:00 p.m.Closing Remarks
3:00 p.m.Adjourn

Additional Information

For more information about this workshop, please contact: ASHWGE@hematology.org.

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