2016 Archived Content

Gene Therapy Breakthroughs Header

Gene therapy has seen its fair share of ups and downs, and yet has continued to progress relentlessly. While the challenges and risks associated with it still remain, there is a new and better understanding of how genes can be effectively manipulated and delivered. With the rise of gene editing tools and enhanced knowledge of targeted delivery, gene therapy is once again being embraced with renewed hope and enthusiasm. Cambridge Healthtech Institute’s conference on Gene Therapy Breakthroughs will bring together leading scientists, clinicians, executives and experts who can collectively disperse information about the impact of recent progress in gene therapy and the areas where it can be applied. The conference will highlight scientific breakthroughs, use of innovative technologies, novel approaches to tackle gene delivery, emerging translational challenges, and will bring together the right people to discuss expected pitfalls and existing opportunities in this field. 

    Final Agenda


    • September 19 Symposium: Strategies for Tackling Rare Genetic Diseases

    • September 20-21 Conference: Gene Therapy Breakthroughs

    • September 21-22 Conference: Advances in Gene Editing and Gene Silencing - Part 2

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    Tuesday, September 20

    7:00 am Registration Open and Morning Coffee


    8:05 Chairperson’s Opening Remarks

    Bryan R. Cullen, Ph.D., James B. Duke Professor of Molecular Genetics and Microbiology and Director, Center for Virology, Duke University

    8:20 AAV for Gene Therapy and Genome Editing

    James Wilson, M.D., Ph.D., Professor, Department of Pathology and Laboratory Medicine, Perelman School of Medicine; Director, Orphan Disease Center and Director, Gene Therapy Program, University of Pennsylvania

    In vivo delivery of nucleic acid therapeutics remains the primary barrier to success. My lab has focused on the use of vectors based on adeno-associated virus (AAV) for achieving success in pre-clinical and clinical applications of gene replacement therapy. Most of the current academic and commercial applications of in vivo gene replacement therapy are based on endogenous AAVs we discovered as latent viral genomes in primates. These vectors are reasonably safe and efficient for application of gene replacement therapy. The emergence of genome editing methods has suggested more precise and effective methods to treat inherited diseases in which genes are silenced or mutations are corrected. AAV vectors have been the most efficient platform for achieving genome editing in vivo. We will review our attempts to achieve therapeutic genome editing in animal models of liver disease using AAV.

    9:20 Using CRISPR/Cas to Target and Destroy Viral DNA Genomes

    Bryan R. Cullen, Ph.D., James B. Duke Professor of Molecular Genetics and Microbiology and Director, Center for Virology, Duke University

    A number of pathogenic human DNA viruses, including HBV, HIV-1 and HSV1, cause chronic diseases in humans that remain refractory to cure, though these diseases can be controlled by antivirals. In addition the DNA virus HPV causes tumors that depend on the continued expression of viral genes. Here, I will present data demonstrating that several of these viruses can be efficiently cleaved and destroyed using viral vectors that express Cas9 and virus-specific guide RNAs, thus providing a potential novel approach to treatment.

    9:50 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

    10:35 Targeted Endonucleases as Antiviral Agents: Promises and Pitfalls

    Keith R. Jerome, M.D., Ph.D., Member, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center; Professor and Head, Virology Division, Department of Laboratory Medicine, University of Washington

    Genome editing offers the prospect of cure for infections such as HIV, hepatitis B virus, herpes simplex, and human papillomavirus, by disruption of essential viral nucleic acids or the human genes encoding receptors needed for viral entry. This talk will highlight the most recent laboratory data and the challenges still ahead in bringing this technology to the clinic.

    11:05 Nucleic Acid Delivery Systems for RNA Therapy and Gene Editing

    Daniel Anderson, Ph.D., Professor, Department of Chemical Engineering, Institute for Medical Engineering & Science, Harvard-MIT Division of Health Sciences & Technology and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

    High throughput, combinatorial approaches have revolutionized small molecule drug discovery. Here we describe our high throughput methods for developing and characterizing RNA delivery and gene editing systems. Libraries of degradable polymers and lipid-like materials have been synthesized, formulated and screened for their ability to deliver RNA, both in vitro and in vivo. A number of delivery formulations have been developed with in vivo efficacy, and show potential applications for the treatment of genetic diseases, viral infections and cancers.

    11:35 PANEL DISCUSSION: CRISPR/Cas: A Realistic and Practical Look at What the Future Could Hold

    Moderator: Bryan R. Cullen, Ph.D., James B. Duke Professor of Molecular Genetics and Microbiology and Director, Center for Virology, Duke University

    Participants: Session Speakers

    Each speaker will spend a few minutes sharing their viewpoints and experiences on where things stand with using the CRISPR/Cas system for in vivo applications. Attendees will have an opportunity to ask questions and share their opinions.

    12:05 pm CRISPR/Cas9 for the Screening of the Human Kinome – A Pilot Study in an Aggressive Pediatric Cancer Cell Line

    Simone T. Sredni, M.D., Ph.D., Research Associate Professor, Neurological Surgery, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago

    The CRISPR-Cas9 system for genome editing is a powerful tool to identify genes involved in vital biological processes. A systematic functional screening of the human kinome has the potential to reveal molecules that are essential for tumor survival, growth, and migration. We will describe our experience using the Invitrogen LentiArray™CRISPR library to mutate 160kinases in a highly malignant pediatric tumor cell line. We will discuss our approach for screening, monitoring of cells lines, and validation.

    12:35 Session Break

    Millipore Sigma12:45 Luncheon Presentation: Building a Better Research Story: Screening with shRNA and CRISPR

    Ryan Raver, Ph.D., Global Product Manager, Functional Genomics, MilliporeSigma

    Parallel RNAi and CRISPR-Cas9 screens have opened up new opportunities for assay development, screening and validation. In partnership with the Wellcome Trust Sanger Institute, MilliporeSigma has developed the first whole genome arrayed CRISPR library. Topics include evaluation of complementary shRNA and CRISPR screens, and the efficacy of each. As each technology has distinct biological processes, the advantages and disadvantages of each for uncovering novel targets will be discussed in detail.

    1:25 Refreshment Break in the Exhibit Hall with Poster Viewing


    2:05 Chairperson’s Remarks

    Joseph D. Gold, Ph.D., Director, Manufacturing, Center for Biomedicine and Genetics, Beckman Research Institute

    2:15 Large-Scale Production of Cell Therapies for Regenerative Medicine

    Joseph D. Gold, Ph.D., Director, Manufacturing, Center for Biomedicine and Genetics, Beckman Research Institute

    There are multiple key decisions to be made in the course of conceptualizing and producing a stem cell-derived therapeutic with profound implications for every step from cell choice to eventual use in clinical trials. I will present lessons learned in the ongoing process of designing a large-scale stem cell-based therapy for heart disease that are relevant to other disease targets and cell sources as well.

    3:00 Directed Evolution of New Viruses for Therapeutic Gene Delivery

    David Schaffer, Ph.D., Professor of Chemical and Biomolecular Engineering, Bioengineering, Molecular and Cell Biology, and Neuroscience; Director, Berkeley Stem Cell Center, University of California, Berkeley

    Adeno-associated viral (AAV) vectors have been increasingly successful in clinical trials; however, viruses face many delivery barriers that limit their efficacy for most disease targets. We have developed directed vector evolution – the iterative genetic diversification of a viral genome and functional selection for desired properties – to engineer novel, optimized AAV vectors for efficient, selective delivery for a range of tissue and disease targets.

    3:45 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

    4:25 Lentiviral Vectors for Gene Therapy

    Manjunath N. Swamy, M.D., Professor of Biomedical Sciences and Co-Director of the Center of Emphasis in Infectious Diseases, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center

    Lentiviral vectors allow transduction of mediators of RNAi and gene editing in a wide variety of cells. We have designed lentiviral vectors to 1) express virtually unlimited numbers of microRNA mimicking shRNAs (shRNA-miRs) using minimal flanking sequence from multiple endogenous miRNAs, 2) transiently express zinc finger nucleases using integrase-deficient vectors and 3) pre-pack Cas9 protein in the viral particles for safer gene editing.

    4:55 AAV Caspid Engineering

    Miguel Sena Esteves, Ph.D., Associate Professor, Department of Neurology, Gene Therapy Center, University of Massachusetts Medical School

    Adeno-associated virus vectors have become the leading platform for development of in vivo gene therapies for neurological diseases. We have developed new AAV vectors for widespread gene delivery to the CNS through vascular infusion in adult animals through peptide grafting and in vivo library selection. These new neurotropic AAVs have achieved CNS-wide silencing of gene expression using gene-specific microRNAs.

    5:25 Welcome Reception in the Exhibit Hall with Poster Viewing

    6:25 End of Day

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    Wednesday, September 21

    7:30 am Registration Open and Morning Coffee


    8:00 Chairperson’s Opening Remarks

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

    8:10 Gene Editing Technologies for the Treatment of Liver Diseases

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

    Efforts have been intensified to develop liver-targeted approaches using novel gene editing technologies, including ZFN, TALEN, CRISPR/Cas and PITCh. While each of these methods utilizes a distinct mechanism at the genomic level, they all are dependent on an efficient delivery system to the target site within the host cell. Clinical trials for liver gene therapy have entered an exciting era and are already showing promise with the development of novel technologies and delivery options.

    8:40 Gene Editing for Generating Exogenic Organs and Cells

    Walter C. Low, Ph.D., Professor and Associate Head for Research, Department of Neurosurgery, Stem Cell Institute, University of Minnesota Medical School

    A major goal of stem cell research is generating organs and cells for repair and replacement in degenerative disorders. Recent advances in gene editing and stem cell biology have converged to demonstrate generating specific organs and types of cells. We have used gene editing technologies to knockout key genes required for the development of the pancreas, liver, skeletal muscle, kidney, and lungs, as well as specific types of neurons, and immune cells. Stem cell complementation in knockout blastocysts for generating targeted organs and cells is discussed.

    9:10 Novel in vivo Genome Editing Technology and Application for Gene Therapy

    Keiichiro Suzuki, Ph.D., Research Associate, Laboratory of Dr. Juan Carlos Izpisua Belmonte, Gene Expression Laboratory, The Salk Institute for Biological Studies

    Non-dividing cells, the major constituents of adult tissues, are inaccessible for targeted knock-in with current technologies. We have developed a robust homology-independent targeted integration (HITI) strategy that allows for efficient targeted knock-in in both dividing and non-dividing cells in vitro and in vivo. Using this method, we achieved the therapeutic efficacy of a rat model of blindness retinitis pigmentosa in vivo.

    9:40 Coffee Break in the Exhibit Hall with Poster Viewing

    10:25 CRISPR in Stem Cell Models of Eye Disease

    Alexander Bassuk, M.D., Ph.D., Associate Professor of Pediatrics, Department of Molecular and Cellular Biology, University of Iowa

    Induced pluripotent stem cells (iPSCs) generated from patient fibroblasts could potentially be used as a source of autologous cells for transplantation in retinal disease. Patient-derived iPSCs, however, would still harbor disease-causing mutations. To generate healthy patient-derived cells, we used CRISPR/Cas9 to precisely repair a point mutation that causes retinal degeneration. This important proof-of-concept finding supports the development of personalized iPSC-based transplantation therapies for retinal disease.

    10:55 CRISPR in Mouse Models of Eye Disease

    Vinit Mahajan, M.D., Ph.D., Assistant Professor of Ophthalmology and Visual Sciences, University of Iowa College of Medicine

    Massive parallel sequencing enables identification of numerous genetic variants, but determining pathogenicity of any one mutation is daunting. The most commonly studied preclinical model of retinal degeneration is homozygous for two different mutations in the same gene. We used the CRISPR/Cas9 gene editing system to identify the causative variant and rescue neurofunction. This is among the first examples of CRISPR-mediated repair in a sensory system.

    11:25 Enjoy Lunch on Your Own

    2:40 Refreshment Break in the Exhibit Hall with Poster Viewing

    3:20 End of Conference

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