Note: Please refer to my previous posts on Tardigrades (Water Bears) from the links below.
Unkillable Water Bears - September 2 , 2022 - https://elakiri.com/threads/unkillable-water-bears.2069775/
Tardigrade Proteins slow metabolism in Human Cells - April 9, 2024 -
https://elakiri.com/threads/tardigrade-proteins-slow-metabolism-in-human-cells.2150953/
We Finally Understand Why Tardigrades Refuse to Die - October 24, 2024 -
https://elakiri.com/threads/we-finally-understand-why-tardigrades-refuse-to-die.2181856/
About 60 percent of all cancer patients receive radiation therapy as part of their treatment. However, this radiation can have severe side effects that often end up being too difficult for patients to tolerate.
Drawing inspiration from a tiny organism that can withstand huge amounts of radiation, researchers at MIT, Brigham and Women’s Hospital, and the University of Iowa have developed a new strategy that may protect patients from this kind of damage. Their approach makes use of a protein from tardigrades, often also called “water bears,” which are usually less than a millimeter in length.
When the researchers injected messenger RNA encoding this protein into mice, they found that it generated enough protein to protect cells’ DNA from radiation-induced damage. If developed for use in humans, this approach could benefit many cancer patients, the researchers say.
Currently, there are very few ways to prevent radiation damage in cancer patients. There are a handful of drugs that can be given to try to reduce the damage, and for prostate cancer patients, a hydrogel can be used to create a physical barrier between the prostate and the rectum during radiation treatment.
For several years, Traverso and Byrne (University of Iowa) have been working on developing new ways to prevent radiation damage. In the new study, they were inspired by the extraordinary survival ability of tardigrades. Found all over the world, usually in aquatic environments, these organisms are well known for their resilience to extreme conditions. Scientists have even sent them into space, where they were shown to survive extreme dehydration and cosmic radiation.
One key component of tardigrades’ defense systems is a unique damage suppressor protein called Dsup, which binds to DNA and helps protect it from radiation-induced damage. This protein plays a major role in tardigrades’ ability to survive radiation doses 2,000 to 3,000 times higher than what a human being can tolerate.
When brainstorming ideas for novel ways to protect cancer patients from radiation, the researchers wondered if they might be able to deliver messenger RNA encoding Dsup to patient tissues before radiation treatment. This mRNA would trigger cells to transiently express the protein, protecting DNA during the treatment. After a few hours, the mRNA and protein would disappear.
For this to work, the researchers needed a way to deliver mRNA that would generate large amounts of protein in the target tissues. They screened libraries of delivery particles containing both polymer and lipid components, which have been used separately to achieve efficient mRNA delivery. From these screens, they identified one polymer-lipid particle that was best-suited for delivery to the colon, and another that was optimized to deliver mRNA to mouth tissue.
“We thought that perhaps by combining these two systems — polymers and lipids — we may be able to get the best of both worlds and get highly potent RNA delivery. And that’s essentially what we saw,” Kirtane says. “One of the strengths of our approach is that we are using a messenger RNA, which just temporarily expresses the protein, so it’s considered far safer than something like DNA, which may be incorporated into the cells’ genome.”
After showing that these particles could successfully deliver mRNA to cells grown in the lab, the researchers tested whether this approach could effectively protect tissue from radiation in a mouse model.
They injected the particles into either the cheek or the rectum several hours before giving a dose of radiation similar to what cancer patients would receive. In these mice, the researchers saw a 50 percent reduction in the amount of double-stranded DNA breaks caused by radiation.
“This study shows great promise and is a really novel idea leveraging natural mechanisms of protection again DNA damage for the purpose of protecting healthy cells during radiation treatments for cancer,” says Ben Ho Park, director of the Vanderbilt-Ingram Cancer Center at Vanderbilt University Medical Center, who was not involved in the study.
Unkillable Water Bears - September 2 , 2022 - https://elakiri.com/threads/unkillable-water-bears.2069775/
Tardigrade Proteins slow metabolism in Human Cells - April 9, 2024 -
https://elakiri.com/threads/tardigrade-proteins-slow-metabolism-in-human-cells.2150953/
We Finally Understand Why Tardigrades Refuse to Die - October 24, 2024 -
https://elakiri.com/threads/we-finally-understand-why-tardigrades-refuse-to-die.2181856/
About 60 percent of all cancer patients receive radiation therapy as part of their treatment. However, this radiation can have severe side effects that often end up being too difficult for patients to tolerate.
Drawing inspiration from a tiny organism that can withstand huge amounts of radiation, researchers at MIT, Brigham and Women’s Hospital, and the University of Iowa have developed a new strategy that may protect patients from this kind of damage. Their approach makes use of a protein from tardigrades, often also called “water bears,” which are usually less than a millimeter in length.
When the researchers injected messenger RNA encoding this protein into mice, they found that it generated enough protein to protect cells’ DNA from radiation-induced damage. If developed for use in humans, this approach could benefit many cancer patients, the researchers say.
Currently, there are very few ways to prevent radiation damage in cancer patients. There are a handful of drugs that can be given to try to reduce the damage, and for prostate cancer patients, a hydrogel can be used to create a physical barrier between the prostate and the rectum during radiation treatment.
For several years, Traverso and Byrne (University of Iowa) have been working on developing new ways to prevent radiation damage. In the new study, they were inspired by the extraordinary survival ability of tardigrades. Found all over the world, usually in aquatic environments, these organisms are well known for their resilience to extreme conditions. Scientists have even sent them into space, where they were shown to survive extreme dehydration and cosmic radiation.
One key component of tardigrades’ defense systems is a unique damage suppressor protein called Dsup, which binds to DNA and helps protect it from radiation-induced damage. This protein plays a major role in tardigrades’ ability to survive radiation doses 2,000 to 3,000 times higher than what a human being can tolerate.
When brainstorming ideas for novel ways to protect cancer patients from radiation, the researchers wondered if they might be able to deliver messenger RNA encoding Dsup to patient tissues before radiation treatment. This mRNA would trigger cells to transiently express the protein, protecting DNA during the treatment. After a few hours, the mRNA and protein would disappear.
For this to work, the researchers needed a way to deliver mRNA that would generate large amounts of protein in the target tissues. They screened libraries of delivery particles containing both polymer and lipid components, which have been used separately to achieve efficient mRNA delivery. From these screens, they identified one polymer-lipid particle that was best-suited for delivery to the colon, and another that was optimized to deliver mRNA to mouth tissue.
“We thought that perhaps by combining these two systems — polymers and lipids — we may be able to get the best of both worlds and get highly potent RNA delivery. And that’s essentially what we saw,” Kirtane says. “One of the strengths of our approach is that we are using a messenger RNA, which just temporarily expresses the protein, so it’s considered far safer than something like DNA, which may be incorporated into the cells’ genome.”
After showing that these particles could successfully deliver mRNA to cells grown in the lab, the researchers tested whether this approach could effectively protect tissue from radiation in a mouse model.
They injected the particles into either the cheek or the rectum several hours before giving a dose of radiation similar to what cancer patients would receive. In these mice, the researchers saw a 50 percent reduction in the amount of double-stranded DNA breaks caused by radiation.
“This study shows great promise and is a really novel idea leveraging natural mechanisms of protection again DNA damage for the purpose of protecting healthy cells during radiation treatments for cancer,” says Ben Ho Park, director of the Vanderbilt-Ingram Cancer Center at Vanderbilt University Medical Center, who was not involved in the study.
