Cambridge Healthtech Institute’s Inaugural

New Frontiers in Gene Editing and Repair

Using CRISPR and Other Gene Editing Techniques to Drive Precision Medicine

March 28, 2019


Gene editing, particularly using the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas system, has very rapidly established its importance as a screening tool in drug discovery, and is now being used for therapeutic purposes as well. Cambridge Healthtech Institute’s inaugural symposium on New Frontiers in Gene Editing and Repair will bring together experts from research and clinical laboratories to talk about how gene editing can be used to engineer precision and accuracy for driving targeted therapies. At the same time, what is being done to overcome some of the inherent challenges related to guide RNA design, delivery and off-target effects associated with gene editing, and some of the alternative approaches and tools being developed, will also be discussed. Experts from pharma/biotech, academia, government labs, and technology/service companies will share their experiences leveraging the utility of gene editing for developing better and safer therapeutics.

Final Agenda


7:30 am Registration and Morning Coffee


8:15 Welcome Remarks from Conference Director

Tanuja Koppal, PhD, Conference Director, Cambridge Healthtech Institute

8:25 Chairperson’s Opening Remarks

Søren Warming, PhD, Senior Scientist, Genentech, Inc., a Member of the Roche Group

8:30 Gene Editing Approaches to the Treatment of Liver Diseases

Clifford Steer, MD, Professor of Medicine and Genetics, Cell Biology and Development; Director, Molecular Gastroenterology Program, University of Minnesota Medical School

Among the novel approaches in gene editing, CRISPR/Cas9 technology has become the most popular, in part due to its ability to carry out gene editing at the target site with great precision. With considerable successes in animal and preclinical studies, CRISPR/Cas9-mediated gene editing has paved the way for its use in human trials, including patients with a variety of liver diseases. Gene editing is a logical therapeutic approach for liver diseases because many of the metabolic and acquired disorders are caused by mutations within a single gene.

9:00 Switchable Genome Editing via Genetic Code Expansion

Yu-Hsuan Tsai, PhD, Lecturer in Chemical Biology, School of Chemistry, Cardiff University

Multiple applications of genome editing by CRISPR-Cas9 necessitate stringent regulation. We have developed heritable Cas9-mediated mammalian genome editing that is acutely controlled by a non-natural amino acid. Using this approach, we demonstrated stringently amino acid dependent, heritable editing of transgenic and native genomic at the onset of mouse embryonic development. This approach promises broad applications, including therapeutic genome editing and gene drives.

9:30 CRISPR Off-Target Analysis in Genetically Engineered Rodents

Søren Warming, PhD, Senior Scientist, Genentech, Inc., a Member of the Roche Group

We generated deep-sequencing data from 81 genome-editing rodent model projects at 1,423 predicted off-target sites and confirmed editing at 32 off-target sites. Using whole-genome sequencing data from ten CRISPR-treated mouse embryos and their genetic parents, we found a total of 43 off-targets. This data was recently published (Nat Methods 2018: 15(7):512-514) and I will discuss how we have implemented our findings into our workflow and provide recommendations for the use of CRISPR in rodent models.

10:00 Networking Coffee Break

10:30 CRISPR: An Evolving Tool for Studying and Eliminating HIV Disease

Will Dampier, PhD, Assistant Professor, Department of Microbiology & Immunology, Center for Molecular Virology & Translational Neuroscience, Drexel University College of Medicine

HIV-1 infects millions of people across the world. While current anti-retroviral therapy manages viral proliferation, the early formation of a persistently integrated latent reservoir is a major cure barrier. CRISPR gene editing provides a potential avenue for addressing this therapeutic limitation. This talk will focus on computational design strategies for overcoming genetic variation inherent in HIV-1 infection in an effort to create broad-spectrum CRISPR targeting strategies.

11:00 Elucidating the Mechanism of Action and Regulatory Circuitry of CRISPR-Directed Gene Editing in Human Cells

Eric B. Kmiec, PhD, Director, Gene Editing Institute; Senior Research Scientist, Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System

CRISPR-directed gene editing is being tested for clinical feasibility. We have taken a decidedly reductionist approach to understanding the regulatory circuitry that surrounds it. Using a human cell-free system, a ribonucleoprotein (RNP) particle and a defined template, we have uncovered regulatory factors that provide guidance for achieving productive outcomes with a level of precision. This system lays the foundation to study the relationships among MMEJ, NHEJ and HDR pathways simultaneously in a controlled reaction environment.

11:30 Additional time for Q&A with Speakers

12:00 pm Enjoy Lunch on Your Own

12:30 Session Break


1:15 Chairperson’s Remarks

Alexandra Hicks, PhD, Executive Director, Hemoglobinopathies, Bioverativ, a Sanofi Company

1:20 Genetic Modification of NK Cells Opens a New Era of Cancer Immunotherapy

Meisam Naeimi Kararoudi, DVM, PhD, Postdoctoral Fellow, Cell Therapy and Cancer Immunotherapy Program, Center for Childhood Cancer and Blood Disorders, Nationwide Children’s Hospital

NK cells have the potential to treat a wide range of cancers, and genetic modification may enhance their potency as cancer immunotherapeutics. Recently, we developed a new strategy for genetic modification of NK cells in which CRISPR/Cas9 elements are introduced as ribonucleoproteins (RNPs) via electroporation, followed by expansion on feeder cells. This method enabled us to genetically modify NK cells with enhanced cytotoxicity against several cancer targets.

1:50 Gene Editing Cancer Cells: A New Frontier in Cell Therapy for Cancer

Khalid Shah, MS, PhD, Director, Center for Stem Cell Therapies and Imaging, Harvard Medical School; Vice Chair of Research, Brigham and Women’s Hospital

We have developed tumor cell surface receptor targeted adult stem cells expressing novel bi-functional immunomodulatory proteins and oncolytic viruses and shown the efficacy of engineered cells in different cancer models. Recently, we have reverse engineered cancer cells using CRISPR/Cas9 technology and demonstrated self-tumor tropism and therapeutic potential of receptor self-targeted engineered cancer cells. This talk considers the current status of cell-based treatments for cancer and provides a rationale for using CRISPR/Cas9 edited cancer cells for treating different cancer types in primary, recurrent, and metastatic settings.

2:20 Networking Refreshment Break

2:40 PANEL DISCUSSION: Rare Diseases - From Simple to Complicated, Complex and Cure

Moderator: Michael N. Liebman, PhD, Managing Director, IPQ Analytics, LLC


Debbie Lin, PhD, Executive Director, Venture Fund Digital Health, Boehringer-Ingelheim

Jon Morris, MD, VP Provider Solutions & CMIO, IQVIA

Durhane Wong-Rieger, President & CEO, Canadian Organization for Rare Disorders

This panel will focus on the complexities of diagnosing and stratifying rare diseases using both traditional clinical observations and the application of digital health methodologies. Rare diseases share many real-world issues with common diseases, but patient numbers limit the application of conventional statistical analyses. Discussion of approaches and examples of how novel methodologies and technologies can improve patient care and drug development will be presented, as well as the stratification of some common diseases into rare disease subtypes.

3:30 FEATURED PRESENTATION: Gene Therapy Projects at NCATS and the NIH Common Fund Somatic Cell Genome Editing Program

Philip John (P.J.) Brooks, PhD, Program Director, Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH)

This talk will cover: Perspectives on gene therapy from the National Center for Advancing Translational Sciences, with an emphasis on platform approaches; the Rare Diseases Clinical Research Network as a clinical trial platform for gene therapy and genome editing; and the NIH Common Fund Program on Somatic Cell Genome Editing.

4:00 Disrupting a BCL11A Enhancer with Zinc Finger Nucleases (ZFNs) for the Potential Treatment of Sickle Cell Disease and Beta Thalassemia

Alexandra Hicks, PhD, Executive Director, Hemoglobinopathies, Bioverativ, a Sanofi Company

High fetal hemoglobin (HbF) levels are associated with asymptomatic sickle cell disease and less severe beta-thalassemia. BIVV-003 is a novel gene editing treatment comprising autologous HSPCs modified with ZFNs targeted to the erythroid-specific enhancer sequence of BCL11A, a key transcriptional regulator of fetal to adult hemoglobin switching. We will present preclinical data showing that the human HSPCs of BIVV-003 are efficiently and reproducibly edited at the BCL11A enhancer with high specificity resulting in reactivation of HbF expression. These edited HSPCs exhibit normal functionality and are capable of long-term engraftment in vivo.

4:30 Paving a Legal Path for Translational Genome Editing

Paul Enríquez, JD, LLM, PhD Candidate, Structural and Molecular Biochemistry, North Carolina State University

CRISPR systems are pushing the frontiers of genome editing applications with remarkable speed. Exciting prospects for revolutionizing personalized medicine and gene therapies are on the horizon. However, uncertainty looms concerning how law and policy will promote or hinder development of this nascent biotechnology. This talk identifies regulatory gaps, examines current challenges and opportunities in the field, and outlines a practical legal path for translating genome editing into the clinic.

5:00 Close of Symposium

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