New Frontiers in Gene Editing will bring together experts from all aspects of basic science and clinical research to talk about how and where gene editing can be best applied. What are the different tools that can be used for gene editing, and what are their strengths and limitations? How does the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas system, compare to Transcription Activator-like Effector Nucleases (TALENs), zinc finger nucleases (ZFNs) and other systems and where are they being used? 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 functional screening, disease modeling, and for creating cell and viral therapies.

Final Agenda

Day 1 | Day 2 | Download Brochure

Wednesday, September 23

11:30 am Registration

12:55 pm Plenary Keynote Program

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

FUNCTIONAL SCREENS USING GENE EDITING

3:25 Chairperson’s Opening Remarks

Bruce R. Conklin M.D., Investigator, Roddenberry Center for Stem Cell Biology and Medicine, Gladstone Institutes and Professor, Division of Genomic Medicine University of California, San Francisco 

3:35 KEYNOTE: Gene Editing and Gene Silencing with CRISPR-Based Systems

Bruce R. Conklin M.D., Investigator, Roddenberry Center for Stem Cell Biology and Medicine, Gladstone Institutes and Professor, Division of Genomic Medicine University of California, San Francisco

We have developed Rare Allele Induction and Detection (RAID), a method that allows for precise base-by-base genome editing in human iPSCs. We are also using CRISPRi to rapidly inactivate genes in iPSCs, to induce disease phenotypes. CRISPRi and RAID will advance genome engineering by allowing human iPSCs to model human genetics, revert disease mutations, and create engineered alleles with unparalleled precision and efficiency.

4:35 CRISPR and RNAi Platforms for Genome-Wide Loss-of-Function Genetic Screens

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

Genome-wide loss-of-function pooled screens provide a direct approach to identify genes regulating biological responses and find new therapeutic targets. While RNAi screens have proven effective, CRISPR/Cas9 provide a newer attractive alternative. To complement our established shRNA screening platform, we have developed similar pooled sgRNA libraries for functional CRISPR knockout screens and ran screens PDX-derived cell lines to compare the performance of each.

5:05 Refreshment Break in the Exhibit Hall with Poster Viewing

5:40 Assay Development for Phenotypic Screening: CRISPR-Mediated Knockout, Knockdown and Sensor Cell Lines

Melissa G. Mendez, Ph.D., Postdoctoral Fellow, Laboratory of Assay Development & Screening Technology (ADST), National Center for Advancing Translational Sciences, NIH

In phenotypic screening, compound structure, titration data and multiple phenotypic readouts are multiplexed across hundreds of thousands of wells per, and across cell models. CRISPR-mediated editing allows these models to be created with deliberate complementarity while maintaining endogenous expression patterns, greatly easing historic restrictions on model selection. We have recreated the hallmark pathobiology of the rare disease Giant Axonal Neuropathy in a cell model system amenable to a variety of screening paradigms.

6:10 Latest Approaches to Genetic Screens with CRISPR Technology

John Doench, Ph.D., Research Scientist, Broad Institute of Harvard and MIT

The ease of programming Cas9 with a sgRNA presents an abundance of potential target sites, but the on-target activity and off-target effects of individual sgRNAs can vary. We will discuss improved models that allow for increased on-target efficacy, metrics for understanding potential off-target sites, and how the combination of these findings can be used to design optimal libraries for genetic screens.

6:40 Close of Day

Day 1 | Day 2 | Download Brochure

Thursday, September 24

7:30 am Registration

8:00 Interactive Breakfast Breakout Discussion Groups

This interactive session provides conference delegates and speakers an opportunity to choose a specific roundtable discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Putting shRNA and CRISPR Screens to The Best Use

Roderick Beijersbergen, Ph.D., Group Leader, Division of Molecular Carcinogenesis, The Netherlands Cancer Institute

Michael Bassik, Ph.D., Assistant Professor, Department of Genetics, Stanford University

• Moving beyond CRISPR; using CRISPRi and CRISPRa as screening tools
• How to select hits from large scale shRNA and CRISPR screens
• shRNA v/s CRISPR-based screening: Selecting the best technology for your question

Using RNAi and CRISPR/Cas9 for Developing In vivo Disease Models

Lukas Dow, Ph.D., Assistant Professor of Biochemistry in Medicine, Department of Medicine, Hematology and Medical Oncology, Sandra and Edward Meyer Cancer Center, Weill Cornell Medical College

Harnessing the Potential of Gene Editing in Stem Cells

Bruce R. Conklin M.D., Investigator, Roddenberry Center for Stem Cell Biology and Medicine, Gladstone Institutes and Professor, Division of Genomic Medicine University of California, San Francisco

• What is the best editing method in different cell types?
• ·How does epigenetic modification alter Cas9 or other platforms?

BUILDING IN VIVO MODELS FOR DRUG DISCOVERY

8:45 Chairperson’s Remarks

 Myung Shin, Ph.D., Senior Principal Scientist, Biology-Discovery, Genetics and Pharmacogenomics, Merck Research Laboratories 

8:55 Genome Editing Animal Models in Drug Discovery

Myung Shin, Ph.D., Senior Principal Scientist, Biology-Discovery, Genetics and Pharmacogenomics, Merck Research Laboratories

Recent advances in genome editing have greatly accelerated and expanded the ability to generate animal models. These tools allow generating mouse models in condensed timeline compared to that of conventional gene-targeting knock-out/knock-in strategies. Moreover, the genome editing methods have expanded the ability to generate animal models beyond mice. In this talk, we will discuss the application of ZFN and CRISPR to generate various animal models for drug discovery programs.

9:25 In vivo Cancer Modeling and Genetic Screening Using CRISPR/Cas9

Sidi Chen, Ph.D., Postdoctoral Fellow, Laboratories of Dr. Phillip A. Sharp and Dr. Feng Zhang, Koch Institute for Integrative Cancer Research at MIT and Broad Institute of Harvard and MIT

Here we describe a genome-wide CRISPR-Cas9-mediated loss-of-function screen in tumor growth and metastasis. We mutagenized a non-metastatic mouse cancer cell line using a genome-scale library. The mutant cell pool rapidly generates metastases when transplanted into immunocompromised mice. Enriched sgRNAs in lung metastases and late stage primary tumors were found to target a small set of genes, suggesting specific loss-of-function mutations drive tumor growth and metastasis.

9:55 FEATURED PRESENTATION: In vivo Chromosome Engineering Using CRISPR-Cas9

Andrea Ventura, M.D., Ph.D., Assistant Member, Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center

We will discuss our experience using somatic genome editing to engineer oncogenic chromosomal rearrangements in vivo. More specifically, we will present the results of our ongoing efforts aimed at modeling cancers driven by chromosomal rearrangements using viral mediated delivery of Crispr-Cas9 to adult animals.

10:25 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Winner Announced

11:10 RNAi and CRISPR/Cas9-Based in vivo Models for Drug Discovery

Christof Fellmann, Ph.D., Postdoctoral Fellow, Laboratory of Dr. Jennifer Doudna, Department of Molecular and Cell Biology, The University of California, Berkeley

Genetically engineered mouse models (GEMMs) are a powerful tool to study disease initiation, treatment response and relapse. By combining CRISPR/Cas9 and “Sensor” validated, tetracycline-regulated “miR-E” shRNA technology, we have developed a fast and scalable platform to generate RNAi GEMMs with reversible gene silencing capability. The synergy of CRISPR/Cas9 and RNAi enabled us to not only model disease pathogenesis, but also mimic drug therapy in mice, providing us capability to perform preclinical studies in vivo.

11:40 In vivo Genome Editing Using Staphylococcus aureus Cas9

Le Cong, Ph.D., Post-doctoral Associate, Laboratory of Dr. Aviv Regev, Broad Institute

The RNA-guided Cas9 nuclease from the bacterial CRISPR/Cas system has been adapted as a powerful tool for facilitating targeted genome editing in eukaryotes. Recently, we have identified an additional small Cas9 nuclease from Staphylococcus aureus that can be packaged with its guide RNA into a single adeno-associated virus (AAV) vector for in vivo applications. We demonstrate the use of this system for effective gene modification in adult animals and further expand the Cas9 toolbox for in vivo genome editing.

12:10 pm Screening with the Sanger Arrayed Lentiviral CRISPR Knockout Library

Shawn Shafer, Ph.D., Market Segment Manager, Functional Genomics, Sigma-Aldrich

12:40 Session Break

12:50 Luncheon Presentation: OriGene, Making the Right Tools for CRISPR Research

Xuan Liu, Ph.D., Senior Director, Marketing, OriGene

CRISPR technology has quickly revolutionized the scientific community. Its simplicity has democratized the genome editing technology and enabled every lab to consider its utility in gene function research. As the largest tool box for gene functional research, OriGene created a large collection of CRISPR-related tools, including various all-in-one vectors for gRNA cloning, donor vector backbones, genome-wide knockout kits, AAVS1 insertion vectors, etc. OriGene’s high quality products will accelerate CRISPR research.

1:40 Refreshment Break in the Exhibit Hall with Poster Viewing

TOWARDS A THERAPEUTIC ENDPOINT

2:15 Chairperson’s Remarks

Matthew Porteus, M.D., Ph.D., Associate Professor, Pediatrics, Stanford University School of Medicine

2:20 Going Native: Exploiting Endogenous CRISPR-Cas Systems for Genome Engineering

Chase Beisel, Ph.D., Assistant Professor, Department of Chemical & Biomolecular Engineering, North Carolina State University

An unexplored avenue is using native CRISPR-Cas systems as convenient tools for the diverse bacteria and archaea that harbor these systems. Here, we describe how the most prevalent type of CRISPR-Cas systems can be exploited for gene regulation, opening new opportunities for genome-wide functional screens and metabolic engineering. These findings also inspired a rapid screen to determine a system’s protospacer adjacent motif, facilitating the adoption of diverse CRISPR-Cas systems for biomolecular research and human therapy.

2:50 Therapeutic Genome Editing for Blood Diseases

Matthew Porteus, M.D., Ph.D., Associate Professor, Pediatrics, Stanford University School of Medicine

There are host of genetic diseases for which allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative. This curative approach has been called “allogeneic gene therapy” because it replaces the genome with a disease causing mutation with a genome that does not have the mutation. The toxicity and complexity of allo-HSCT precludes it being widely used but is the proof-of-concept that autologous HSCT using gene corrected cells could also cure such diseases without the associated complexity and toxicity.

3:20 Session Break

3:30 Using CRISPR as a Tool for Enabling Active Genetics

Ethan Bier, Ph.D., Professor, Division of Biological Sciences, University of California, San Diego

The high efficiency with which we have observed autocatalytic allelic conversion by a cas9/gRNA-based mutagenesis system in fruit flies has broad applications to controlling vector borne disease and invasive pest species. The implications of this new form of active genetics for human health, basic research, and gene drive systems will be discussed.

4:00 Inducible Genome Editing for Disease Modeling

Lukas Dow, Ph.D., Assistant Professor of Biochemistry in Medicine, Department of Medicine, Hematology and Medical Oncology, Sandra and Edward Meyer Cancer Center, Weill Cornell Medical College

CRISPR/Cas9-based genome editing enables the rapid genetic manipulation of any genomic locus without the need for gene targeting by homologous recombination. We will discuss our efforts to develop conditional transgenic approaches that allow temporal control of CRISPR/Cas9 activity for inducible genome editing in adult mice. The inducible CRISPR (iCRISPR) system can be used effectively to create biallelic mutation in multiple target loci and thus, provides a flexible and fast platform for disease modeling in vivo.

4:30 Q&A With Session Speakers

5:00 Close of Conference

Day 1 | Day 2 | Download Brochure