CRISPR (Clusters of Regularly Interspaced Short Palindromic Repeats) is a specialized region of DNA comprised of two distinct characteristics including presence of nucleotide repeats and spacers. The term CRISPR is used interchangeably with CRISPR-Cas9. Cas9 (CRISPR-associated) is a protein that acts like molecular scissors cutting strands of DNA. It is basically a system inherent in bacterial DNA that allows them to recognize and fend off attackers, usually viruses. The technique came into existence from studies exploring the natural defense mechanisms of single-celled microorganisms. 2012 saw the transformation of bacterial CRISPR-Cas9 into a simple, programmable genome-editing tool as revealed by research papers published in Science and PNAS. Use of CRISPR-Cas9 to edit human cells in an experimental setting was first reported in 2013 by researchers from the laboratories of George Church and Feng Zhang at the Broad Institute of the Massachusetts Institute of Technology and Harvard. Chinese researchers experimentally modified the gene linked to the blood disorder beta thalassemia in year 2015 and followed by making genes resistant to HIV infection in 2016.
CRISPR is a simple, fast, cheap, powerful, and unique genome editing tool used in genome engineering. CRISPR technology involved a patent battle involving Harvard/MIT and the University of California Berkeley that started in 2014 and finally led to the granting of the patent to Broad Institute of Harvard and MIT. Two researchers viewed as CRISPR’s pioneers in the scientific community are Jennifer Doudna and Emmanuelle Charpentier, who have won the $3 million Breakthrough Prize in life sciences in 2015, the $500,000 Gruber Genetics Prize in 2015, and the $450,000 Japan Prize in 2017. At present the potential applications, apart from therapeutics, include use in crop improvement, and in the food and agricultural industry for engineering probiotic cultures and vaccinating industrial cultures. A new breakthrough in genome engineering addresses the transformation of living cells into archival data storage devices by using a large population of bacteria and using their own genome as a biological hard drive for storing digital information.
Various potential therapeutic applications of CRISPR may include the elimination of mutations linked to breast cancer, ovarian cancer, cystic fibrosis; use in treatment of AIDS by removing the HIV virus. CRISPR technology may permit the correction of genetic mutations linked to disease that are discovered in human embryos during preimplantation genetic diagnosis (PGD). It has already been used in sight restoration in blind rd1 mice by correcting a mutation in the Pde6b gene; and in deletion of entire targeted chromosomes in case of aneuploidies. Scientists are working to identify new strategies for developing treatments for neurodegenerative diseases like Alzheimer’s and Parkinson’s by using CRISPR-based platform. At this time China is in the lead as far as clinical trials are concerned and may be the first to try editing the genomes of cells inside the body to eliminate cancer-causing human papilloma virus. Also in China, more than a dozen trials involving disabling of PD-1 with CRISPR and its possible application in conditions such as breast, prostate, bladder, esophageal, kidney, colorectal and Epstein-Barr virus-associated cancers. In the USA, clinical trials using another genome editing tool zinc finger nucleases for the addition of genes to liver cells for treatment of hemophilia B, and Hurler and Hunter syndromes is under way. In the United Kingdom trials are in the planning stages with UCART19 cells created with one of the older gene-editing methods. China and USA are also planning two and one UCART19 trials respectively.
Some of the above mentioned technologies will be discussed at GTCbio’s 7th Genomics and Big Data Summit that will be held on September 26-27, 2017 in San Diego, CA, and the speakers for the track entitled “CRISPR & Genome Engineering” include the following:
• Ron Weiss, Professor, Director, Synthetic Biology Center, MIT
Dr. Ron’s research interest is in Synthetic biology. His research experience mainly includes assembly and delivery of genetic circuits; mammalian synthetic transcriptional regulation; Micro-bio-robotic communication; and in vivo biosensors.
• Jonathan Chesnut, Sr. Director, Synthetic Biology R&D, Thermo Fisher Scientific
Dr. Jonathan has led the development of various prokaryotic and mammalian cell cloning and expression systems. He currently leads the group with focus on developing tools for the entire Synthetic Biology and Cell Engineering workflow, specifically Bioinformatics, Genome Editing, and Cellular Analytics.
• CB Gurumurthy, Associate Professor, Developmental Neuroscience, University of Nebraska Medical Center
Dr. Gurumurthy has varied experience with expertise in veterinary virology; drug discovery research; cancer biology; and mouse molecular genetics. His research interests include improvement and development of novel genome engineering technologies.
• Garrett Rettig, Sr. Staff Scientist, Molecular Genetics, Integrated DNA Technologies
Dr. Garrett Rettig is primarily involved in high-throughput in vitro screening of siRNAs, and other oligonucleotide-based technologies in cell biology applications. Most recently, he has been focused on developing CRISPR technologies at IDT and applying Next Generation Sequencing strategies to detecting on-target and off-target editing events.
• Edward Rebar, VP, Technology, Sangamo therapeutics
Dr. Edward has over 10 years of industry experience in early and late stage clinical development in a broad range of disease areas including rare diseases, ultra-rare diseases, oncology and infectious diseases. Dr. Edward has led protocol development and regulatory interaction for global phase 3 program in Pompe disease at BioMarin Pharmaceuticals Inc.; and clinical science team for two product candidates, including Xolair® at Genentech.
• Daniel Anderson, Assoc. Prof., Chemical Engineering and Institute for Medical Engineering and Science, Massachusetts Institute of Technology
Dr. Daniel is a leading researcher in the field of nanotherapeutics and biomaterials. His laboratory is focused on developing new materials for medicine and has pioneered the development of smart biomaterials. His work covers a range of areas, including medical devices, cell therapy, drug delivery, gene therapy and material science.
• Eric Ostertag, CEO, Poseida Therapeutics
Dr. Eric has over 12 years of executive management experience. He has received scientific and clinical awards from the American Society of Human Genetics and the American Society for Apheresis. Prior to Poseida, Dr. Eric was co-founder, CEO of PhenoTech, & Vindico; founder, CEO of Transposagen. He has published nearly twenty peer-reviewed articles and reviews in the field of mobile DNA.
• Joe Bondy-Denomy, Faculty Fellow, Department of Microbiology & Immunology, UCSF
Dr. Joe has studied interactions between bacteriophages and their host bacteria, focusing on the effects of lysogeny and the CRISPR-Cas immune system. His lab is currently focused on studying the roles of CRISPR-Cas immune systems in their host organisms, discovering novel CRISPR-Cas functions and identifying ways in which these systems interact with bacteriophages.
We invite you to join us at the 7th Genomics and Big Data Summit in San Diego on September 26-27.