2016 Archived Content

Understanding CRISPR Mechanisms and Applications Header

Gene editing is rapidly progressing from being a research/screening tool to one that promises important applications downstream in drug development, cell and gene therapy. Cambridge Healthtech Institute’s symposium on Understanding CRISPR: Mechanisms to Applications will bring together experts to talk about how gene editing works and where it can be best applied. How does the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas system, compare to other gene editing tools? What do we now know about the biology of CRISPR and what lessons have we learnt from working with RNA interference (RNAi)? Scientists will discuss new findings in CRISPR mechanisms and share their experiences leveraging the utility of CRISPR-based gene editing.

Final Agenda


• September 19 Symposium: Understanding CRISPR: Mechanisms and Applications

• September 19 Short Course: Introduction to Gene Editing

• 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

Monday, September 19

7:00 am Registration Open and Morning Coffee


8:00 Chairperson’s Opening Remarks

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

8:10 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.

8:40 Getting from Alpha to Omega: Successfully Conceptualizing, Starting and Finishing CRISPR/Cas Screens

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

For certain molecular targets, to unravel the underlying biology of loss-of-function studies, it is simply not enough to potently knockdown the protein. In some cases, a complete functional knockout is called for. Here we summarize our early experiences, highlighting the strengths of this new powerful system but also calling attention to technical areas which need to be addressed and further improved as the technology moves deeper into the mainstream.

9:10 Genome Editing-Enabled HTS Assays for Genetically Inherited Disease Drug Discovery

James Inglese, Ph.D., Head Assay Development & Screening Technologies, National Center for Advancing Translational Sciences, National Institutes of Health

The targeted precision of genome editing was used in combination with advances in reporter gene design to modify the genetic loci of neurologic target genes to create HTS assays for compound library interrogation. Our goal was to identify transcriptionally active pharmacological agents acting by a variety of mechanisms, including through chromatin co-regulators accessible by our assay design. Specific case studies will serve to illustrate progress and findings to date.

9:40 Use of CRISPR and Other Genomic Technologies to Advance Drug Discovery

Namjin Chung, Ph.D., Head, Functional Genomics Platform, Discovery Research, AbbVie, Inc.

Advances in CRISPR gene editing and genomics technologies are rapidly changing biopharmaceutical R&D landscape, from target ID and validation, to drug mechanism of action, and to translational science. We will use vignettes of various genomics research applications within AbbVie R&D environment as a witness to this paradigm shift currently ongoing in the drug industry.

10:10 Coffee Break

10:40 Vignettes From the Bench: CRISPR Engineering Lymphoma Lines

Arthur L. Shaffer, III, Ph.D., Staff Scientist, Laboratory of Dr. Louis Staudt, Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health

CRISPR/CAS9 technology is a powerful tool that permits the easy exploration of human genetics using cell line models. Our lab focuses on understanding the wiring of lymphoma cells in an effort to discover new therapeutic options. I will relate some lessons we’ve learned as we adapt CRISPR/Cas9 to the study of lymphoma.

11:10 PANEL DISCUSSION: Will Interference from CRISPR Silence RNAi?

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

Participants: Session Speakers

Each speaker will spend a few minutes sharing their viewpoints and experiences using CRISPR/Cas system for functional screening and complementing it with RNAi screening. Attendees will have an opportunity to ask questions and share their opinions.

11:40 Enjoy Lunch on Your Own


1:40 Chairperson’s Opening Remarks

James Inglese, Ph.D., Head Assay Development & Screening Technologies, National Center for Advancing Translational Sciences, National Institutes of Health

1:50 MicroRNA Target Site Editing of Chondrocyte Master-Regulators in Primary Human Cells Using CRISPR-Cas9

Christine Seidl, Ph.D., Post-Doctoral Research Associate, Cell Signaling, Kennedy Institute of Rheumatology, Oxford University

MicroRNAs (miR) are important regulators of gene expression. Frequently, several potential target sites are located on a transcript but only one constitutes the dominant regulatory element. In this talk, a method will be discussed that allows for endogenous miR target site identification in primary human chondrocytes using CRISPR-Cas9 without the need of clonal selection of edited cells.

2:20 Massively Parallel Combinatorial Genetic Perturbation Screening with CRISPR-Cas9 in Human Cells

Cheryl H. Cui, Ph.D. Candidate, Harvard-MIT Division of Health Science and Technology, MIT

The systematic analysis of combinatorial gene functions is labor-intensive and challenging to scale. Our platform enables massively parallel screening of barcoded combinatorial gene perturbations in human cells. This technology leverages the simplicity of the CRISPR-Cas9 system for multiplexed targeting of specific genomic loci and the scalability of CombiGEM (Combinatorial Genetics En Masse)-based DNA assembly to construct barcoded combinatorial genetic libraries that can be quantified with high-throughput sequencing.

2:50 The Scientist’s Guide to CRISPR Law

Paul Enríquez, J.D., LL.M., Ph.D. Candidate, Structural and Molecular Biochemistry, North Carolina State University

CRISPR systems are revolutionizing science and biotechnology. However, great uncertainty exists surrounding how the law will treat this nascent biotechnology. This talk provides an overview of the key regulatory issues every CRISPR scientist should know. Drawing parallels from stem cells and gene therapy, the talk highlights the importance of law and policy in fostering CRIPSR-based research, and makes recommendations for scientists studying CRISPR mechanisms and applications.

3:20 Close of Symposium

* Separate registration required for Short Courses, Symposia, Training Seminar

Stay On and Attend - SC12: Introduction to Gene Editing