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University of Basel

CRISPR/Cas9 – Opportunity or Risk, Rolf Zeller?

Text: Rolf Zeller

Discovered just a few years ago, the CRISPR/Cas9 method promises new possibilities for editing the genome of living creatures. While some see this as an opportunity, others focus on the risks of this efficient technology.

Prof. Rolf Zeller. (Illustration: Studio Nippoldt)
Rolf Zeller is Professor of Anatomy and Embryology in the Department of Biomedicine at the University of Basel. An evolutionary biologist, his research focuses on the signal interactions and gene networks that control organ development in vertebrates.

CRISPR/Cas9 technology enables the germline of plants and animals, including humans, to be modified simply and with great precision without leaving traces in the genome. This system was discovered in bacteria, which use it to cut up the DNA of invading viruses. When studying this defense mechanism, the researchers working under Emmanuelle Charpentier and Jennifer Doudna discovered that the method is universal and can be used to cut DNA strands at specific points.

The CRISPR/Cas9 complex consists of «guide» RNA, which defines the interface, and the Cas9 enzyme, which cuts the DNA. This method also works on the basis that eucaryotic cells (fungi, plants, and animals) quickly repair cut DNA strands. To specifically edit a gene, a piece of synthetic DNA is introduced into the cells, along with the CRISPR/Cas9, that overlaps with the interface and codes the desired genetic change. This sequence serves as a template for the DNA repair and leads to the desired change being incorporated into the genome – so-called «genome editing».

One advantage the CRISPR/Cas9 system has over traditional transgenic methods is that no foreign DNA is incorporated into the genome. The US authorities have therefore decided that if the genome of a cultivated mushroom is edited with CRISPR/Cas9, it does not need to be labelled as genetically modified. Plant biology uses CRISPR/Cas9 technology to modify cultivated plants much more specifically than in traditional cross-breeding. Many cultivated plants lost their natural resistance gene during yield optimization and no longer grow in barren soil; one goal is therefore to repair or replace defective or missing genes.

CRISPR/Cas9 has quickly become the preferred method for genetic studies in the life sciences too. Cell- and animal-based models for analyzing underlying processes and diseases can now be generated much more quickly and in an unprecedented variety of species.

CRISPR/Cas9 is also expected to finally make the longed-for breakthrough in gene therapy. In the most promising strategy, (stem) cells from the patient’s own body are isolated and genome editing is used to correct their genetic defects. Repaired cells can only be transplanted back into patients following molecular testing, so the hope is to minimize the risk of unwanted side effects. This strategy has already been successfully tested in animal models for various, sometimes fatal genetic diseases. Clinical studies on this subject are to start in the near future. An initial study of germline editing in nonviable human embryos was published in 2015. This showed that CRISPR/Cas9 is too inefficient for germline manipulation and can lead to potentially dangerous side effects, particularly if the CRISPR/Cas9 cuts the DNA in the wrong place. These rare effects could lead to the activation of cancer genes; intensive work is therefore underway to minimize these effects through improved enzymes.

The use of genome editing for human embryos has prompted a global debate about intervening in the human germline. The manipulation of human embryos is prohibited in Switzerland, while other countries permit its application for research purposes. We must be open about both the many opportunities and the risks of using CRISPR/Cas9 in plants, animals, and humans. As with all therapeutic applications, there is a residual risk that must be weighed against the anticipated benefits.

More articles in the current issue of UNI NOVA.

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