Sunday, October 8
The Revolution in Gene Editing Using CRISPR/Cas9: Medical Miracle or Brave New World?
1.0 CME/CE Credit
During this plenary, you will learn to:
- Describe the CRISPR/Cas9 approach to gene editing and why it represents such a radical advance beyond all previous approaches to gene therapy
- Review present and near-future clinical applications of the technology in genetic, neoplastic, and immunologic diseases
- Discuss the myriad ethical challenges that will inevitably accompany the range of potential uses of the technology to patients and human embryos
Gene therapy for hereditary disorders and cancer has long been the “holy grail” of molecular medicine. Despite decades of effort, it has remained elusive for all but a few special applications (for example, certain leukemias and degenerative retinal disorders). Major obstacles to current gene therapy include toxicity of the viral vectors; difficulty targeting the replacement in the tissue of interest; random integration of the replacement gene into the genome, producing off-target effects; imprecise dosing; and frequent loss or dilution of the replacement gene as cells in the target tissue replicate. In recent years, a radically different approach has evolved, one that involves not gene replacement but in situ gene editing. Several methods were developed for accomplishing this, but until recently they were expensive, cumbersome, inefficient, and inaccurate. That has all changed with the development of an ingenious system based on an existing property of adaptive immunity in certain species of bacteria, dubbed CRISPR/Cas9.
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and Cas9 is one of several genes associated with the system. Together they provide precise targeting and destruction of invading nucleic acids that have entered the bacterial cell. Remarkably, the same system can be introduced into living eukaryotic cells to target any gene of interest, using synthesized complementary “guide RNAs.” The method is easy to use and far more efficient and accurate than any of the previous approaches. It also is remarkably versatile in that it can be used for gene deletion, gene replacement, gene regulation, or gene editing (adding or removing mutations); and it works in all species, including humans, and all tissues.
CRISPR/Cas9 already has proven to be an invaluable research tool for studying gene function and regulation and for creating mutant and knockout models of genetic disorders in vitro and in vivo. Now we seem to be on the cusp of applying it to human embryos, germ cells, tumors, and patients. The technology’s ease of use has evoked concern in some quarters over its potential to alter the human genome permanently, ushering in a new era of eugenics and “designer humans.” Many urge caution or even an outright moratorium on its use in living patients and especially embryos, where the edited gene would enter the germline and be preserved in subsequent generations.
Join us to hear nationally recognized experts in a panel discussion on the fundamentals of the CRISPR/Cas9 technology, its powers and pitfalls, and its ongoing use in genetic and oncology research. Panelists will explore the potential medical applications in genetic disease and cancer and share the initial experiments conducted and the practical outcomes to emerge thus far. They also will address the challenging ethical issues raised by this technology as well as discuss the future role of pathologists in testing, monitoring, and gatekeeping the performance of gene editing in patients and biopsy tissues. Don’t miss this thought-provoking session!
Wayne W. Grody, MD, PhD, FCAP, Moderator