Now you see it, now you don’t:

From transgenes to the new age of genome editing

Wilhelm Gruissem

Richard HurdFig and Sage

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Genetically modified (GM) crops are now grown in 26 countries and more than 10% of the agricultural land

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For crops such as maize, soybean or sugar beet,the adoption of GM traits is nearly 100%

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GM crops can be tracked because of the traits provided by the transgenes, which has recently led to several class action lawsuits

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But what if new traits in crops and animals cannot be tracked anymore because endogenous genes have been edited?

Developing new traits is now possible using the bacterial CRISPR/Cas RNA-enzyme to introduce targeted mutations

in cells of other organisms

The Cas-enzym and the guide-RNA can be adapted to any DNA sequence, such that the complex can cut the DNA at targeted and precisely defined sites

The cell repairs the cut in the DNA but often not correctly, leading to mutations.

https://www.mirusbio.com/applications/crispr-cas-transfectionCRISPR/Cas has a strong advantage over other mutagenesis methods using chemicals or radiation, which are often used in crop breeding:

• Exact targeting or the desired gene (or genes) • Precise recognition of the cleavage site in the target DNA

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CRISPR/Cas was originally discovered as a central RNA-guided enzyme for the immunity of bacteria against the infection with viruses

Immunization

Immunity

Bacteria virus (bacteriophage) on the outer membrane of a bacterialcell shortly before injecting its DNA. The invading DNA is recognizedby the bacterium and destroyed. Short regions of the invading DNAare integrated into the bacterial genome and used to detect theDNA again in future invasions. Marraffini, Nature 2015

Shutterstock

CRISPR

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Martin Jinek (now at the University of Zurich), Jennifer Doudna and Emmanuelle Charpentier discovered in 2012 that the enzyme Cas9 can

be used for RNA-programmed genome editing

Paul-Ehrlich-Preisin 2016

Jinek et al. (2012) Science 337:816-821

Jennifer Doudna (UC Berkeley) and Emmanuelle Charpentier (now Helmholtz Center for Infection

Biology) receiving the 2015 Breakthrough Prize

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Every day we eat fruits, vegetables and cereals with quality traits that were generated using mutagenesis breeding—

now these mutations can be generated by genome editing

Today we use nearly 4’000 mutated crop varieties in agricultural production worldwide

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Graphiken von Transparenz Gentechnik (http://www.transgen.de)

Genome DNA can be cut precisely usingthe guide-RNA and the Cas-enzyme thatfunctions like a pair of scissors.

The cell recognizes the cut DNA andactivates DNA repair mechanisms. Theserepair mechanisms can result in differentoutcomes (genome editing).

CRISPR/Cas is now used as a new tool for genome editing and gene replacement without the need for transgenes

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Now you see it, now you don’t:

From transgenes to the new age of genome editing

What are the implications of genome editing for

• A legal framework for regulatory decisions and approvals?

• Protection of intellectual property and new traits?

• Traceability of crops and animals with genome-edited traits?

• Risks associated with the agricultural production of genome-edited crops?

• Potential for lawsuits if non-traceable genome-edited traits are marketed?

• Risk management by the insurance industry?

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The plant breeder

Large and diversified germplasm

The farmer

Stable crop production

The consumer

Affordable, high quality, healthy products

Genome editing has significant potential to accelerate breeding of new crop varieties with improved qualities, environmental

sustainability, and resilience to climate change

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