Straight From The Scientist: Jon Chesnut on CRISPR versus TALEN

Tucked within an exhibit in San Diego’s Reuben H. Fleet Science Center is a cardboard cutout of Jon Chesnut, Senior Director of R&D for Synthetic Biology and Sample Prep. A mainstay of Southern California’s “biotech beach,” Chesnut credits his undergrad years at UCSD as the genesis of a dynamic career in the life sciences. “I always liked science and tinkering with things,” he enthuses. Following grad school and a post-doctoral fellowship, Chesnut landed at Invitrogen in 1995. He spent his early days conducting molecular biology research and development and eventually led teams developing innovative cloning technologies, such as TOPO PCR Cloning and Gateway Cloning. Afterwards, stepping into the gene editing arena was a natural undertaking. On genome editing tools such as TALEN and CRISPR, Chesnut now provides thought leadership pertinent to the dialogue surrounding an industry breakthrough topic. Fresh from a synbio media blitz, we catch up with Chesnut and get him to elaborate on the multi-faceted value of “engineering a cell to allow it do something it normally doesn’t.” Join us as we hear straight from the scientist:

Q:  Last year, you wrote a couple articles on CRISPR versus TALEN. Is TALEN getting phased out?

A:  No, in fact we have a program to relaunch TALENs as a genome editing tool which could be used just like CRISPR.  We can now easily make TALENs that perform comparably or better than CRISPR and are focusing on using them to edit parts of the genome where CRISPR is either inefficient or completely non-functional.

Q:  What’s the first step a researcher should take when it comes to determining which gene editing tool to use?

A:  Technically, for gene knock outs, one could choose either tool.  Overall, CRISPR may have slightly higher cutting efficiency than TALENs and it’s efficient to make arrays of CRISPR guide RNAs that allow library-type screening.  TALENs also can do a fine job but it’s not quite as straight forward to make a large array of TALEN pairs.  If a researcher wants to do an edit, where there will be a repair of a mutation or insertion of DNA at a specific locus in a gene, TALENs may be a good bet.  CRISPR targeting is dependent on the availability of a short ‘PAM’ sequence which can limit their utility for editing.  If your target locus is more than 8-10 bases away from the nearest PAM, we’re finding that TALENS (which can be directed anywhere in the genome) are often the best tool.  Also, if a researcher is interested in using their genome editing workflow in a commercial enterprise, Thermo Fisher Scientific can provide a clear path, whereas the CRISPR IP landscape is not clear yet.

Q:  Where do you see the future of genome editing going?

A:  I think we can separate the future of genome editing into three areas:

1)  Cellular and gene therapy. A lot has been written about engineering cells to treat diseases like sickle cell anemia and even HIV using various gene editing approaches.  Now we’re seeing immunotherapy applications, like CAR T-cell approaches, being used to successfully treat some cancers.  These approaches rely on engineering cells with various tools, including CRISPR and TALENs.

2)  Cell and animal model development.  Many of our customers are interested in creating new cell lines and animals (like mice and zebra fish) that model diseases, like cancer, for use in drug screening and development.  We anticipate significant growth in engineered cell lines, specifically in pharma, for use as more physiologically relevant models for disease.  Lowering the bar for creation of models will lead the way to more relevant and complex functional genomics assay systems which promise to give the researcher a clearer insight into the mechanisms of disease.  This, in turn, should allow the development of better therapies and cures.

3)  Agriculture.  Both TALENs and CRISPR are being widely used to engineer plants to facilitate new trait development.  This essentially speeds up the natural process of selective breeding in many cases.  In the end the promise is that these new tools will foster the development of new, more robust crops that can be used to more efficiently feed and fuel the growing world population.

Q:  Finally, our most burning question—do you really have a life-sized cardboard cutout at the Museum of Man?

A:  That was a fun one.  There were a couple years where I was a research fellow in the Corporate Research Lab (Life Tech days) where I was scouting new technologies and had a small research lab.  Life Tech was asked to participate in a stem cell exhibit so I got to travel down there to help them design the technical part of the exhibit.  I was on my last visit to review it just prior to the opening when the lead curator asked me to put on a lab coat for a short photo op.  It took all of two minutes and resulted in the cardboard cutout of me in the ‘lab’ part of the exhibit. It’s been there for almost five years and I get continuous comments (and some good natured flak) about it.  My kids really got a kick out of it!

Interested in hearing more from Jon Chesnut? Check out these articles:
Genetic Engineering and Biotechnology News (GEN): Analyzing TALEN vs CRISPR
Bioscience Technology: CRISPR: A Gene-Editing Tool to Rule Them All? Not Necessarily

For more on CRISPR and TALEN, visit our new Gene Editing Learning Center.
For Research Use Only. Not for use in diagnostic procedures.

Sources:
http://www.thermofisher.com/us/en/home/life-science/genome-editing.html
http://www.thermofisher.com/us/en/home/life-science/genome-editing/genome-editing-learning-center.html