Sunday, November 1, 2015

Why Genome Editing is So Remarkable

Genetic engineering of crops is undergoing a revolution, and it is being led by a new suite of techniques collectively called genome editing.  

Genome editing takes advantage of two components: a natural bacterial enzyme that cuts DNA, and a “guide” molecule of RNA that matches the site in the plant’s DNA where the cut is to be made.  Working together in a cell, these two components allow the biotechnologist to have much more control over the genetic changes taking place in the plant. 

Although I am interested in how genome editing works, I am especially interested in how it differs from older methods of genetic engineering.  Here are three key differences.

1.      Genome editing can produce changes in precisely targeted genes.  With older techniques of genetic engineering, one could insert specific and well-characterized genes into a plant.  However, one had no control over where in the plant’s genetics the new gene landed…or how many copies were inserted.  This was not a fatal limitation.  However, the “collateral damage” to the plant’s genome from gene insertion requires that many plants must be engineered and thoroughly tested in hopes of finding a plant that performs as desired.  But with genome editing, the biotechnologist can choose where and what kind of genetic change s/he wishes, resulting in much more control over the process of genetic engineering.  This is a very big deal.  Genome editing can still produce off-target changes in the plant’s genome, but its error rate is commonly quite low (Woo and colleagues, 2015).  Furthermore, off-target effects of genome editing are considered comparable to those that occur through conventional breeding (EFSA, 2012).  And as always in breeding, one tests the resulting plants to determine if any undesirable changes have occurred.  In the case of genetic engineering, testing is extensive and includes molecular genetic analyses; analyses of chemical composition; evaluation for allergen production and for toxicity; testing in greenhouses, growth chambers, and the field; and other tests.

2.      Genetic changes from genome editing sometimes cannot be distinguished from naturally occurring mutation.  First, understand that mutations are quite natural and occur all the time in living organisms.  In the case of genome editing, genetic changes can be as modest as a single-nucleotide change in a targeted gene.  This is like changing one letter (a single typo) in a specific sentence in an entire book.   a change of one nucleotide is the most precise and minimal change that is physically possible in a plant’s DNA.  Such a change is so minimal that scientists simply cannot distinguish such a change from a mutation that occurred naturally.  There would be no way to tell whether humans or Nature caused a genetic change of one nucleotide.  

3.      Genome editing can be done in ways that leave no trace of “foreign DNA” behind in the engineered plant.  None.  It can be impossible to tell that the plant was ever engineered.  Thus, genome editing allows us to engineer plants in a minimally invasive and minimally disruptive way, leaving no trace of laboratory manipulation.  For a recent example, see Woo and colleagues (2015).  These authors never even used DNA in the genome-editing process. 

Genome editing is widely regarded by biologists as a profoundly important scientific advance.  It is being used very heavily in medical research, and it is expected to provide numerous beneficial outcomes for human health.  Crop scientists are also using genome-editing techniques for research as well as plant gene engineering.

Crop scientists see great value in these techniques, particularly for the development of crops that address challenges to agricultural sustainability.  Some of the sustainability challenges that might be addressed using genome editing include: reducing pesticide use by controlling pests and diseases with genetics instead of pesticides; improving how efficiently plants use fertilizer and water, thus having less impact on the environment; improving nutritional qualities of foods, which has obvious social value; and many other beneficial outcomes.  In developing countries, genome editing will very likely be another tool for local scientists to address food security challenges, as some are currently doing using older techniques of genetic engineering. 

Genome editing can make precise genetic changes that cannot be distinguished from natural genetic changes; it can potentially be done without any DNA; and it can be done without leaving any trace of foreign DNA.  Even to a seasoned biologist like me, this is mind-blowing.  This is not the world of the gene gun, shooting foreign DNA into plants, with no control over where in the plant’s genome the gene went.  It is a new world, a world with much more knowledge, more rapid scientific advances, and more targeted tools to use genetics in ways that enhance the sustainability of our food system. 

Genome editing brings many benefits but it also complicates the regulatory picture.  If a crop variety engineered by genome editing cannot be distinguished from one that was not engineered, can it be regulated?  Should it be regulated?

At the University of Kentucky, it is part of our mission to provide the scientific information the public needs in order to make informed policy decisions.  The field of genetic engineering is changing so rapidly that it is difficult for scientists to remain up-to-date, let alone the general public.  That’s one reason I started this blog—to do my small part to contribute to public discourse about our rapidly changing world of science in order to empower informed decision-making in our journey towards sustainability of our food system.

Update on 6 Nov 2015:
The German Federal Agency for Nature Conservation has ruled that crops created using genome editing will "fall under the European Directive for GMOs."  This ruling may lead the way for other countries to make similar rulings.

Update on 17 Nov 2015: 
"The Swedish Board of Agriculture has, after questions from researchers in UmeĆ„ and Uppsala in Sweden, confirmed the interpretation that some plants in which the genome has been edited using the CRISPR-Cas9 technology do not fall under the European GMO definition."  

Update on 2 Dec 2015:  New study shows that off-target mutations can be significant with CRISPR-Cas9, but that they can be greatly reduced by rationally engineering the enzyme used.

Update on 6 Jan 2016:   
This trend of reducing non-target edits with Cas9 by improving the site-directed nuclease continues with the recent Nature paper entitled, "High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects."

·        EFSA. 2012. Scientific opinion addressing the safety assessment of plants developed using zinc finger nuclease 3 and other site-directed nucleases with similar function.  Report of the European Food Safety Authority Panel on Genetically Modified Organisms.
·        Woo and colleagues, 2015. DNA-free genome editing in plants with preassembled CRISPR-Cas9 ribonucleoproteins. Nature Biotechnology doi:10.1038/nbt.3389

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