Space based CRISPR gene-editing to protect astronauts from radiation damage of Deep-space missionss

Deep-space and long-duration missions, where both crew members and spacecraft no longer benefit from the protection of Earth’s magnetic fields, are considered high risk for adverse radiation impacts.  Aircraft flying at altitude, at about 30,000 feet and above, also are starting to experience radiation-induced effects. “There are 500 times more neutrons at 30,000 feet than there are on the ground,” points out Aitech’s Romaniuk.

Outside the protective cover of the Earth’s atmosphere, the solar system is filled with radiation. The natural space environment consists of electrons and protons trapped by Earth’s magnetic field, protons and small amount of heavy nuclei produced by Solar events, and heavy nuclei, i.e. cosmic rays produced outside the Solar system.

One of the main health concerns with space travel is radiation exposure. Deep-space missions, going beyond the inner planets, or even just one long mission to Mars and back, will be pushing the limits of what we know. It’s also approaching the estimated lifetime limits of radiation for human exposure.

Damage to an organism’s DNA can occur during normal biological processes or as a result of environmental causes, such as UV light. In humans and other animals, damaged DNA can lead to cancer. Fortunately, cells have several different natural strategies by which damaged DNA can be repaired. On Earth, the body can repair double-strand breaks by adding and deleting DNA bases, or re-joining the two pieces without altering them.

Chris Mason, a geneticist and associate professor of physiology and biophysics at Weill Cornell University in New York, has investigated the genetic effects of spaceflight and how humans might overcome these challenges to expand our species farther into the solar system.  If, for example, scientists could figure out a way to make human cells more resilient to the effects of radiation, astronauts could remain healthier for longer durations in space. Theoretically, this type of technology could also be used to combat the effects of radiation on healthy cells during cancer treatments on Earth, Mason noted.

One way that scientists could alter future astronauts is through epigenetic engineering, which essentially means that they would “turn on or off” the expression of specific genes, Mason explained. Alternatively, One of the (strangest) ways that we might protect future astronauts on missions to places like Mars, Mason said, might involve the DNA of tardigrades, tiny micro-animals that can survive the most extreme conditions, even the vacuum of space! Researchers are exploring how to combine the DNA of other species, namely tardigrades, with human cells to make them more resistant to the harmful effects of spaceflight, like radiation.

This wild concept was explored in a 2016 paper, and Mason and his team aim to build upon that research to see if, by using the DNA of ultra-resilient tardigrades, they could protect astronauts from the harmful effects of spaceflight. Genetically editing humans for space travel would likely be a part of natural changes to the human physiology that could occur after living on Mars for a number of years, Mason said. “It’s not if we evolve; it’s when we evolve,” he added.

Scientists are also exploring CRISPR gene-editing technology, or CAR T-cell therapies, in which immune cells are re-engineered to fight cancer — might be used to help astronauts better withstand the rigors of spaceflight.

Astronauts demonstrate CRISPR/Cas9 genome editing in space in June 2021

Astronauts traveling outside of Earth’s protective atmosphere face increased risk of DNA damage due to the ionizing radiation that permeates space. Therefore, which specific DNA-repair strategies are employed by the body in space may be particularly important. Previous work suggests that microgravity conditions may influence this choice, raising concerns that repair might not be adequate. However, technological and safety obstacles have so far limited investigation into the issue. “Understanding whether one type of repair is less error-prone has important implications,” study co-author Sarah Wallace, a microbiologist at NASA’s Johnson Space Center (JSC) in Houston, said in a statement. (The four Minnesota students are co-authors as well.)

The first CRISPR experiment to take place in space shows that DNA can repair itself in microgravity. Stahl-Rommel and colleagues have developed a new method for studying DNA repair in yeast cells that can be conducted entirely in space. The technique uses CRISPR/Cas9 genome editing technology to create precise damage to DNA strands so that DNA repair mechanisms can then be observed in better detail than would be possible with non-specific damage via radiation or other causes. The method focuses on a particularly harmful type of DNA damage known as a double-strand break. In a recent paper published in the journal PLOS One, researchers explained how the DNA was restored to its original order. The introduction of CRISPR in space and the first successful genome manipulation on the ISS extends the possibilities for future DNA repair experiments, researchers said.

Genes In Space-6 was proposed by four Minnesota students as part of a national contest in 2018 that challenged kids in grades seven through 12 to design a DNA analysis experiment. Aarthi Vijayakumar, Michelle Sung, Rebecca Li and David Li designed the experiment as they thought about the increased risk of cancer in astronauts. The increased exposure to radiation in space has the potential to damage the DNA of humans.  Before the Genes In Space-6 experiment, however, these processes had not been studied in microgravity.

“It’s not just that the team successfully deployed novel technologies like CRISPR genome editing, PCR, and nanopore sequencing in an extreme environment, but also that we were able to integrate them into a functionally complete biotechnology workflow applicable to the study of DNA repair and other fundamental cellular processes in microgravity,” said senior author Sebastian Kraves. “These developments fill this team with hope in humanity’s renewed quest to explore and inhabit the vast expanse of space.”

Such knowledge could be beneficial to astronauts — for example, by helping mission planners determine whether more radiation shielding is required. According to Wallace, it’s “important to gain this understanding to help ensure that we are protecting the crew and helping them recover in the best possible way.”

References and Resources also include:

https://www.space.com/genetically-engineer-astronauts-missions-mars-protect-radiation.html

https://www.space.com/genetically-engineer-astronauts-missions-mars-protect-radiation.html