Image of a C. elegans expressing two genes (shown in purple and green) which were incorporated into the genome of the worm using the TARDIS approach. Image credit: Megan J. Moerdyk-Schauwecker (CC BY 4.0)
Transgenesis – the ability to insert foreign genetic material (known as transgenes) in to the genome of an organism – has revolutionized biological research. This approach has made it possible for scientists to study the role of specific genes and to produce animal models which mimic aspects of human diseases.
For transgenes to be maintained and passed down to future generations, they must be introduced into germ cells which will go on to form the egg and sperm of the organism. However, despite advances in genetic engineering, this process (called ‘specific transgenesis’) is still laborious and time-consuming, and limits researchers to working with only a small number of known DNA sequences at a time.
In contrast, ‘exploratory transgenesis’ – where dozens of transgenes from a library of DNA sequences are introduced simultaneously into multiple individuals – is more efficient and allows for more large-scale experiments. However, this approach can only be done with single-celled organisms like bacteria, and remains virtually impossible in laboratory animals like worms or mice.
Stevenson et al. therefore set out to boost the efficiency of exploratory transgenesis in a commonly used laboratory animal, the roundworm Caenorhabditis elegans. To do this, they used the ‘library’ principle of exploratory transgenesis in order to develop a new resource called TARDIS (short for, Transgenic Arrays Resulting in Diversity of Integrated Sequences).
First, Stevenson et al. genetically engineered worms to carry a ‘landing site’ for foreign DNA. Next, a library of transgenes and a mechanism which cuts pieces of DNA and pastes them into the landing site were introduced into the germ cells of these worms using traditional methods. The worms were then bred to generate a large population of offspring that had inherited this array of foreign DNA sequences. Finally, the ‘cut and paste’ mechanism was switched on and a random transgene was inserted into the landing site in the genome. This resulted in thousands of worms which each had a unique genetic modification that can be passed on to future generations.
These results show for the first time that larger-scale transgenesis experiments are possible in multi-cellular animals. In the future, Stevenson et al. hope that TARDIS can be adapted to different organisms and allow researchers to carry out experiments that were not previously possible.
