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The ‘Ubiquitous’ Potential of Gene Editing

One of the winners of the Canada Gairdner International Award for his work on CRISPR talks about its possible world-altering impact.

 |  Transcript [PDF]

If you were to ask a biologist what they though the most significant discovery of the past decade was, many of them would probably say CRISPR.

In fact, CRISPR (pronounced “crisper”) has been in the news so much, both for the bitter patent dispute surrounding its discovery and for its potency in gene editing, that you’d probably be hard-pressed to find anyone who hasn’t heard of it.

In 2016, Jennifer Doudna, Emmanuelle Charpentier, Rodolphe Barrangou, Philippe Horvath, and Feng Zhang won the Canada Gairdner International Award for their work on the CRISPR system.

But apart from its fame and its catchy name, what exactly is CRISPR and what does it do?

You might be surprised to learn that CRISPR is actually an acronym for Clustered Regularly Interspaced Short Palindromic Repeats – a mouthful that basically means a very recognizable repeating DNA sequence.

In bacteria, these sequences act as a sort of primitive immune system, recognizing matching foreign viral DNA and chopping it up using an enzyme called Cas9.

CRISPR sequences were first discovered and documented in the 1980s, but it wasn’t until 2012 that researchers realized they could change the recognition sequence for Cas9, and essentially cut DNA at any location of their choosing. Natural DNA repair mechanisms can then be harnessed to repair the cut in the DNA, adding or mutating any portion into a designer DNA sequence.

“CRISPR technology is repackaging the biology of CRISPR-Cas systems in bacteria and turning into a technology, a tool,” says Barrangou, a biologist at North Carolina State University.

The implications of this are huge: CRISPR could be used to change any DNA sequences precisely and accurately. This includes curing genetic diseases in humans, making disease resistant crops, wiping out whole populations of malaria-carrying mosquitoes, just to name a few applications.

When Science Magazine named CRISPR its “Breakthrough of the Year” in 2015, they stated “it’s only slightly hyperbolic to say that if scientists can dream of a genetic manipulation, CRISPR can now make it happen.”

Barrangou believes that CRISPR has been able to revolutionize, not just science and business, but society as a whole.

“It has had a ubiquitous impact on a very short timeline across many parts of consumers’ and patients’ lives.”

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Rodolphe Barrangou is an Associate Professor in the Department of Food, Bioprocessing and Nutrition Sciences at North Carolina State University, a NC State University Scholar, and the Todd R. Klaenhammer Distinguished Scholar in Probiotics Research. Dr. Barrangou is also an associate member of the Microbiology graduate program, the Biotechnology graduate program, the Functional Genomics graduate program, and the Center for Integrative Medicine. Dr. Barrangou is also an adjunct member of the Food Science Department at the Pennsylvania State University.

His CRISPR laboratory focuses on the evolution and functions of CRISPR-Cas systems, and their use for bacterial genotyping, building prokaryotic immunity, and Cas9-mediated genome editing in lactic acid bacteria used in food manufacturing.

Dr. Barrangou earned a BS in Biological Sciences from the Rene Descartes University in Paris, France; a MS in Biological Engineering from the University of Technology in Compiegne, France; a MS in Food Science from NC State University; a PhD in Genomics from NC State University; and a MBA from the University of Wisconsin-Madison. Dr. Barrangou and colleagues at DuPont established the biological role of CRISPR-Cas systems in adaptive immunity in bacteria, and used CRISPR-based technologies for bacterial genotyping of industrial cultures, and for the vaccination of dairy cultures against bacteriophages. After nine years in R&D and M&A at Danisco and DuPont, he joined the faculty at NC State University in 2013.

Dr. Barrangou is the recipient of the 2014 NC State Alumni Association Outstanding Research Award, and of the 2015 NC State Faculty Scholars Award. He has been on the Thomson Reuters Highly Cited Researchers list in 2014 and 2015. Dr. Barrangou is on the board of directors of Caribou Biosciences, a co-founder and member of the Scientific Advisory Board of Intellia Therapeutics, and a founding investor of Locus Biosciences.

Dr. Barrangou has published numerous articles on CRISPR-Cas systems and their use since 2005, including establishing their role as bacterial immune systems, and exploiting them for industrial applications. Following the initial work unraveling the biological function of CRISPR arrays and cas genes, subsequent studies and collaborative efforts identified PAMs as critical sequences for phage DNA targeting, showed that Cas9 is an endonuclease which can cleave plasmid and phage DNA, and provided the first proof of concept that CRISPR can be reprogrammed and transferred heterologously. Dr. Barrangou also established and co-hosted five international CRISPR meetings, and edited the first book on CRISPR-Cas systems.