2016 Archived Content

Advances in Gene Editing and Gene Silencing - Part 1 Header

Cambridge Healthtech Institute’s 13th annual two-part conference on Advances in Gene Editing and Gene Silencing will cover the latest in the use of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9-based gene editing and RNA interference (RNAi) for use in drug discovery and for developing novel drug therapies.

Part 1 will cover the use of CRISPR/Cas9 and RNAi for identifying new drug targets and therapies. It will bring together experts from all aspects of basic science and clinical research to talk about how and where gene editing and RNAi can be best applied. What are the different tools that can be used and what are their strengths and limitations? How does the CRISPR/Cas system compare to RNAi and other gene editing tools, such as Transcription Activator-like Effector Nucleases (TALENs) and zinc finger nucleases (ZFNs), and do they have any complementary uses? Scientists and clinicians from pharma/biotech as well as from academic and government labs will share their experiences leveraging the utility of gene editing for target discovery, disease modeling, and for creating cell and viral therapies.

Final Agenda


• September 19 Short Course: Introduction to Gene Editing

• September 19 Symposium: Understanding CRISPR: Mechanisms and Applications

• September 20-21 Conference: Advances in Gene Editing and Gene Silencing - Part 1

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

• September 21 Short Course: Functional Screening Strategies Using CRISPR and RNAi

Day 1 | Day 2 | Download Brochure

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 Assistant 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

Ralph Garippa, Ph.D., Director, RNAi Core Facility, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center

2:15 Comparing Arrayed siRNA and CRISPR Approaches Towards Functional Genomics Screening

Scott Martin, Ph.D., Group Lead, Functional Genomics, Genentech Inc.

RNAi has been a workhorse for loss-of-function screening. Although powerful, RNAi is hampered by false positives. New screening technologies based on CRISPR/Cas9 appear less prone to off-target effects. CRISPR/Cas9 screens are conducted in pooled formats. However, this format is not amenable to many assays. In an effort to expand its utility, we explored the use of arrayed CRISPR/Cas9 screening with synthetic CRISPR RNAs.

2:45 Use of CRISPR/Cas9-Based Gene Editing to Model and Treat Retinal Degenerative Disease

Donald Zack, M.D., Ph.D., Guerrieri Professor of Genetic Engineering and Molecular Ophthalmology, Johns Hopkins University

The combination of human stem cell retinal modeling, CRISPR/Cas9 genome editing, and high content screening technology provides unparalleled opportunities for the study of retinal biology, disease modeling, drug screening, and the development of novel gene therapy-based treatment approaches. The use of these technologies to model and identify new targets for diseases involving retinal ganglion cells, photoreceptors, and retinal pigment epithelial cells will be discussed.

HP sm3:15 HP Inkjet Technology for Enhancing Gene Editing Experiments

Erica Squires, Ph.D., Senior Applications Scientist, HP Inc.

HP inkjet technology is now being used around the world to easily and precisely dispense both small molecules and biomolecules directly into microwell plates for dose response, qPCR miniaturization and other low volume (down to 11 pL) dispensing applications. Join us for presentation of and active dialogue about research case studies. Learn how fellow drug discovery researchers are accelerating learning through an improved understanding of dose response, MOA, and drug-drug synergies.

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

4:25 Harnessing the Versatile CRISPR-Cas9 Systems for Cancer Modeling Platforms

Geoffrey Bartholomeusz, Ph.D., Associate Professor and Director, Target Identification and Validation Program, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

The specificity of the CRISPR/Cas9-based gene editing technology derived from the microbial defense system is driving innovative applications from basic biology to biotechnology and medicine. To successfully utilize this gene editing system to further understand the operations of complex genomes, it is imperative to minimize interfering off target biological mechanisms. We highlight such outcome identified during the optimization of our CRISPR systems.

4:55 Technology Panel: Trends in CRISPR & RNAi Technologies

Moderator: Ralph Garippa, Ph.D., Director, RNAi Core Facility, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center


Louise Baskin, Senior Product Manager, Dharmacon, GE Healthcare

Paul Diehl, Ph.D., Director, Business Development, Cellecta Inc.

Others to be announced


This panel will bring together 4-5 technical experts from leading technology and service companies to discuss trends and improvements in library design, assay reagents and platforms, and data analysis tools that users can expect to see in the near future.

5:25 Welcome Reception in the Exhibit Hall

6:25 End of Day

Day 1 | Day 2 | Download Brochure

Wednesday, September 21

7:30 am Registration Open and Morning Coffee


8:00 Chairperson’s Opening Remarks

TJ Cradick , Ph.D., Head of Genome Editing, CRISPR Therapeutics

8:10 Functional Genomics Using CRISPR-Cas9: Technology and Applications

Neville Sanjana, Ph.D., Core Faculty Member, New York Genome Center and Assistant Professor, Department of Biology & Center for Genomics and Systems Biology, New York University

The easy programmability of CRISPR/Cas9 suggests a new way to interrogate gene function at the DNA level instead of the transcript level. By combining genome engineering with functional genomic screens, we have developed genome-wide libraries for negative and positive selection screening in human and mouse cells. In addition, we have developed techniques for adapting CRISPR screens into noncoding regions of the genome, where it can be challenging to identify functional elements.

8:40 Therapeutic Gene Editing With CRISPR/Cas9

TJ Cradick , Ph.D., Head of Genome Editing, CRISPR Therapeutics

CRISPR-Cas9 systems are programmable nucleases that can be designed to precisely edit the genome to correct disease-causing mutations. CRISPR/Cas systems have enabled a wide range of editing methods in humans and also have enabled genome editing in a long list of plant and animal species. CRISPR/Cas systems are being optimized to drive gene editing. Bioinformatics and design strategies are used to improve and ensure specificity. We will also discuss the use of new CRISPR ortholog systems.

9:10 Towards Combinatorial Drug Discovery: Mining Heterogenous Phenotypes from Large Scale RNAi/Drug Perturbations

Arvind Rao, Ph.D., Assistant Professor, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center

In this talk, we will outline methodologies and share our experiences for the interpretation of cellular phenotypes obtained via high throughput microscopy on drug screens in patient-derived glioma cell lines as well as of Triple negative breast tumors, in 3D culture. The large volume and heterogeneity in cellular phenotypes across the population make this a challenging task. We will also describe frameworks to quantitatively interpret such heterogeneity and prioritize hits (genes from RNAi, drugs from screens).

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

Day 1 | Day 2 | Download Brochure

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Advances in Gene Editing and Gene Silencing - Part 2 Header