Before new methods such as CRISPR/Cas gene scissors are applied, older methods of genetic engineering are often used to introduce the gene scissors into the genetic material of the target organism. This can trigger specific, unwanted changes. In addition, the pattern of genetic modification caused by the new methods is often unique and cannot be achieved with conventional breeding. This also applies to cases in which no additional genes are inserted into the genome.
Scientists working for the US company Calyxt have targeted a group of gluten proteins (gliadins) in wheat that are thought to cause inflammatory bowel diseases (celiac disease). These genes occur within a large family of genes that are present in so-called gene clusters (i.e. in multiple copies) at different locations in the genome. So far, conventional breeding has not been able to reduce the large number of genes and gene copies. With the help of the CRISPR/Cas gene scissors, scientists succeeded for the first time in 2018 in switching off a large number of these genes: 35 of 45 genes that produce gliadins were 'switched off'. The result is a unique pattern of genetic modification in wheat. However, this can also trigger unintended biological properties, e.g. changes in ingredients. For this reason, these plants must be examined in detail to determine risks, even if no additional genes have been inserted to achieve this new gene combination.
There were several stages involved in altering the plants: first, transgenic wheat plants were produced using older genetic engineering methods (i.e. the so-called gene gun). The reason: the protein (enzyme) for the gene scissors must first be built into the plants. For this, a bacterial gene for the formation of the enzyme has to be inserted into the genome of the plants. Only in a second step is the new genetic engineering method (i.e. genome editing) used to 'cut' the respective genes so that they lose their function. This two-stage process is typical for gene scissors applications, which must always be introduced into the cells before becoming active. Such procedures have been applied to almost all genome-edited plants that are so far registered or approved for cultivation in the USA. One consequence: components of the transgenes (including those from the bacteria) are also present in the plants, which the scientists attempt to remove at a later stage in breeding. In addition, the 'shotgun method' commonly used in older genetic engineering often triggers a variety of other unwanted changes in the genome. New substances can emerge that are not intended and are difficult to discover.
This example shows: (1) Plants that are changed using the new genetic engineering techniques must be carefully examined for unwanted changes. All stages of the respective process must be included. (2) In addition, the genome-edited plants often show gene combinations and properties that are difficult or impossible to achieve with conventional breeding. Risks to people and the environment need to be carefully examined.