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.
http://gain.fas.usda.gov/Recent%20GAIN%20Publications/CRISPR%20and%20other%20NBT%E2%80%99s%20classified%20as%20GMO%E2%80%98s_Berlin_Germany_10-30-2015.pdf.
Update on 17 Nov 2015:
"The Swedish Board of Agriculture has, after questions from
researchers in UmeƄ 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." http://www.upsc.se/about-upsc/news/4815-green-light-in-the-tunnel-swedish-board-of-agriculture-a-crispr-cas9-mutant-but-not-a-gmo.html
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. http://www.sciencemag.org/content/early/2015/11/30/science.aad5227.abstract
Update on 6 Jan 2016:
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. http://www.sciencemag.org/content/early/2015/11/30/science.aad5227.abstract
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."
Citations
Citations
·
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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