CRISPR/Cas9 That’s Out of This World

CRISPR/Cas 9 in space: the final frontier? With more astronauts embarking on space explorations (and an obsession for commercial space travel in billionaire circles), there is a growing need to tackle the risk of DNA damage caused by ionizing radiation outside the Earth’s protective atmosphere. Researchers have now developed a system that can study DNA repair in yeast cells in space (1) – so we spoke to senior researcher, Sebastian Kraves, to find out more.

What inspired you to develop a CRISPR/Cas9 gene editing system for use in space?
The idea was developed by a team of high school students who participated in the 2018 Genes in Space competition, in which young students propose their ideas for a DNA experiment that will help advance space exploration. While still in high school, the students conducted biology research at the University of Minnesota. One of them, David Li (now an undergraduate student at MIT), was working with CRISPR/Cas9. After coming across the Genes in Space competition online and reading about the NASA Twin Study, the group became interested in studying DNA damage and repair in space – and thought that CRISPR/Cas9 would be the perfect tool.

During background research, the students and I found that previous studies on the effects of microgravity on DNA repair were limited to using simulated microgravity or inducing breaks on Earth before studying repair in space. We wanted to overcome these limitations by designing an experiment that would allow scientists to damage DNA and observe it repairing itself entirely in space.

How does the system work – and how did you modify it for space?
The elegance of this study is that astronauts can trigger DNA lesions in a controlled manner using the CRISPR gene editing system. CRISPR allows us to target the DNA damage to a particular gene that, when disrupted and repaired, results in a visible color change in the cells. This color shift allowed the astronauts in our study to report back that the technique was working, which they later confirmed with molecular tools (PCR and DNA sequencing).

Did you encounter any challenges in the development process?
We first needed develop the ability to transform and genetically engineer organisms in space. This represented a significant hurdle, but we were lucky to have a talented multidisciplinary team spanning MIT, NASA Johnson Space Center, miniPCR bio, and Boeing. It was no small task to adapt protocols that are routine on Earth’s molecular biology laboratories for space, but our team had previously developed the expertise to enable several of these steps during missions. This time, we had the chance to sequence all of the steps into a complete molecular biology workflow that represents a significant advance – and could enable a plethora of future investigations in the microgravity environment of the International Space Station.

What’s next for the research?
Now that the necessary tools have been validated on the station and the experimental design has been tested, the experiment can be repeated and expanded to a large enough sample size to draw valuable conclusions about how DNA repair is altered in space. This has huge implications for the DNA repair that occurs in astronauts exposed to ionizing radiation for long periods and can inform protective measures and future medical advancements for astronauts returning from spaceflight.

However, although the current study is an important milestone in space biology, the data we obtained aren’t yet sufficient to answer the question the students initially posed in their application to the Genes in Space contest – how is DNA repair pathway choice impacted by microgravity? Expanding this experiment to generate enough data for us to really be able to understand DNA repair choice and the effects of microgravity on DNA repair in space would be a great next step. An important long-term goal is to use this information to find effective ways of mitigating the impact of microgravity on DNA repair to lower the risks to future space travelers.