CRISPR-Cas – accurate DNA modification

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CRISPR-Cas – accurate DNA modification

CRISPR-Cas is a new technology that enables genetic material of viruses, bacteria, cells, plants and animals to be changed relatively simply, very accurately and efficiently. This can be done by making genetic changes that result in altered properties, or by adding entirely new genetic information.

The CRISPR-Cas technique is currently attracting political interest because of its many possible uses for plants, humans and animals.

Questions and answers about CRISPR-Cas

What does CRISPR-Cas mean?

  • CRISPR - Clustered Regularly Interspaced Palindromic Repeats
  • Cas – CRISPR-associated genes & proteins

It is present in the genomes of 40% of bacteria and 85% of Archaea ('archaebacteria'). CRISPR-Cas is an anti-virus system possessed by bacteria and archaea and there is a huge diversity of CRISPR-Cas systems.

Researcher Ruud de Maagd explains: "In the past, you had to design
a different protein for each genetic adaptation – you could think of it as like having to develop a new sat nav for every journey. With CRISPR/Cas, you can use the same sat nav each time; you just have to type in a different address."

How can we usefully employ CRISPR-Cas?

We can use CRISPR-Cas to prevent infectious diseases such as malaria in humans by genetically modifying malaria mosquitoes.

Animal diseases can also be prevented. For example, African swine fever is deadly to domesticated pigs, whereas wild boars barely display any symptoms. By adding this gene, we can make domesticated pigs resistant.

Birth defects can be prevented and animal welfare improved in livestock production – for instance, with polled cows.

In plants, the production of compounds such as fats and oils can be adjusted very precisely, so that the plants produce the best ingredients. And wheat gluten can be modified so that coeliac patients can safely eat wheat and wheat products.

We can also turn off particular genes. Disabling the gene CD163 means pigs are no longer affected by the PRRS virus, a respiratory infection. In plants, we can turn off genes that predispose them to disease. For instance, we can develop potato varieties which are not susceptible to phtophthora (NL), so farmers will need to resort to chemicals less in order to combat diseases.

See also the presentation by Martien Groenen, Professor of Animal Genomics:

  • Genome editing in (farm) animals: opportunities and limitations - Royal Netherlands Academy of Arts and Sciences (KNAW) lecture - 7 Sep 2017

What issues are encountered in the research?

CRISPR-Cas allows us to make targeted changes to a genome. This does mean we need to know exactly which change we want to make. For example, most of the features selected for in breeding are controlled by hundreds of genes. There are very few characteristics for which a single specific mutation is responsible, such as the absence of horns.

There are different situations:

  • a genetic variant occurs with a low frequency in the population (e.g. polled cows)
  • a genetic variant occurs with a positive effect known from another species (e.g. African swine fever: deadly to domesticated pigs whereas wild boars barely display dymptoms. By incorporating this gene, we can make domesticated pigs resistant.)
  • the genetic variant does not occur (as far as it is known) - e.g. by disabling the gene CD163, pigs are no longer affected by the PRRS virus, a respiratory infection.

What are the risks?

There is much debate about the risks of these new breeding techniques. There is particular concern about the unknown
long-term effects of the techniques. Laboratories are taking all kinds of safety measures in order to make sure that material cannot leave the lab. By working under strictly controlled conditions, they are minimising the risks as far as possible.

There is also concern that the benefits of the new techniques should not fall exclusively to large companies but should also be enjoyed by small farmers. This inclusiveness principle is also an issue with other classic breeding techniques.

Some companies also seek to attach the ‘natural’ claim, which is highly valued in the marketing world, to products which are the result of new breeding techniques. This ethical debate is being broadly conducted, for example stimulated by the European Synergene project, with the Rathenau Institute organising the debate.

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