The famous CRISPR / Cas9 technology has found its way into the most unusual laboratory of mankind: Researchers have developed a method for using gene scissors on the International Space Station ISS and successfully tested it there. With the help of the gene scissors, astronauts can now study how cells repair damaged DNA in space. The findings could, among other things, benefit space travelers better health care.
UV light, radioactivity or free radicals – biological processes and various environmental influences are constantly gnawing at the genetic material in our body cells. In the worst case scenario, this damage can lead to the development of cancer. Therefore, maintenance measures must be carried out constantly in our body: Cells have various natural strategies with which they can repair damaged DNA. In the case of astronauts, efficient patchwork is particularly important: Since they are outside the protective earth’s atmosphere, they are exposed to increased ionizing radiation and thus an increased risk of genetic damage.
So far, however, it is unclear to what extent the DNA repair system reacts to the changed gravity conditions in space. There is evidence that microgravity conditions affect the manner in which it is repaired. This raises concerns that, in addition to the higher stress, the genetic self-healing powers of space travelers could be impaired. Further research on this topic has so far been restricted by technological and safety-related obstacles: The use of investigation techniques in which genetic material is experimentally damaged, for example by radiation, is problematic on the ISS. In addition, they lead to unspecific damage to the DNA, so that repair processes cannot be specifically investigated.
Tricky laboratory work in the balance
That is why the researchers around Sarah Stahl-Rommel from NASA’s Johnson Space Center in Houston have now developed a new investigation method for use in space. It is based on the CRISPR / Cas9 genome editing technology. The specificity in the DNA cutting function made this tool famous. It is based on the combination of a gene segment with the target information with an enzyme that acts as a pair of scissors. This team is able to specifically bind to certain DNA sequences in the genome and to cut them. In this way, experimental damage to the DNA can also be produced in a targeted manner in order to investigate subsequent repair mechanisms, the researchers explain. Their focus is on particularly dangerous DNA damage: the so-called double-strand breaks.
The scientists use the unicellular yeast Saccharomyces cerevisiae for their Space-CRISPR / Cas9 process. Because these eukaryotic organisms are easy to handle and have a nucleus like ours and similar DNA repair mechanisms. As the researchers report, the main challenge in developing the method was to adapt the methods used on Earth for the CRISPR / Cas9 technology to weightlessness. One can easily imagine that many reagents, processes and working methods, such as those used in earthly laboratory work, function poorly or not at all in a suspended state.
Promising success
“The specialist knowledge of our team ultimately led to a concept through which complex science can also be carried out beyond the boundaries of the earth,” says Stahl-Rommel. Among other things, through the economical use of reagents, some of which are premixed and frozen in the process, the researchers succeeded in developing a practicable method for CRISPR genome editing in microgravity. “In this way, this technology, as well as the subsequent PCR processes and nanopore sequencing, could be implemented in the extreme environment. We were also able to integrate the process into a biotechnological workflow that can be used for investigating DNA repair and other basic cellular processes in weightlessness, ”says co-author Sebastian Kraves from the participating company MiniPCR in Cambridge.
The actual suitability for practice was documented by the successful use of the method on the ISS: It was shown by easily recognizable color changes in the yeast cells, which are associated with the concept of genetic manipulation used. “The genome of these organisms was edited with CRISPR / Cas9 to cause breaks in the DNA, followed by the DNA repair processes that allowed growth, and finally the resulting DNA was sequenced – all on board the ISS,” sums up Co- Author Sarah Castro-Wallace from the Johnson Space Center.
As the researchers explain, the success represents a proof of concept – the process can now become a cornerstone for extensive research into DNA repair mechanisms in space. “It’s a big step forward for space biology,” said Castro-Wallace. According to them, the method can also be further refined and modified in order to better simulate the complex DNA damage caused by ionizing radiation. In addition, it could also form the basis for the investigation of numerous other molecular biological questions that are related to long-term stays in space. “This looks very promising with regard to the endeavors of mankind to continue to explore space and to live there too,” says Kraves.
Source: PLOS, technical article: PLOS ONE, doi: 10.1371 / journal.pone.0253403