CRISPR-Cas9 Gene Editing, Mechanism and after therapy

The Nobel Prize in Medicine and Physiology was awarded to James Allison and Tasuku Honjo for the pioneering research in developing the tools that now allow cancer to be detected and treated before it develops and kills, creating what has been called “a revolution in cancer treatment” On Tuesday, Allison and colleagues published a paper in Science about the methods they’ve used for developing the cancer therapies.

Crispr Experiments

The group genetically manipulated a tumor in mice to eliminate the stem cells that form tumors. After introducing the genetic modification, the mice were injected with the radiation therapy. Within a week, 95 percent of the mice who received the radiation therapy were in remission. In a second experiment, scientists used the same approach to treat cancers that were already in the animals, which was completed in two weeks.

How CRISPR works?

The difference between the cells that were genetically modified and the ones that were not used in the current studies is that the genetically altered cells carried an extra piece of protein known as a tumor suppressor, or tumor repeller. After the radiation therapy was applied, the cells containing the extra piece of protein died off, freeing up the stem cells to come back and grow new tumors.

Two previous studies of applying these “spearhead” therapies in mice have shown them to be effective, although they are not able to take over the entire tumor and kill the animal. But when the researchers applied the therapy to single cells in each animal, the animals grew worse. These results have raised questions about using Crispr for targeted therapy.

“Perhaps the primary issue is that the tumor cells seem to go back to their original state of lung cancer, whereas the added genetic change seems to be associated with killing the other cells within the tumor,” said James G. Schubert, a scientist at the Vanderbilt University Center for Cancer Immunology and Inflammation.

After therapy

Once the therapy is complete, the tissue is evaluated for evidence of cancers that have disappeared from the animal. Since that tissue was initially irradiated, it is unlikely that any cancer cells would have been killed during the radiation therapy. The tumor samples are then kept in a refrigerated room and examined at the Vanderbilt Institute for Cancer Immunology and Inflammation.

Even if the tumors are smaller than before the therapy was applied, scientists are able to detect the cancer cells by testing them for a number of specific proteins.

“This process takes a lot of time, but it’s a very, very accurate way of finding those tumor cells that were killed and thus are not alive anymore,” said Jerome M. Eliahou, one of the authors of the paper and a researcher in the Institute. “These cell lines can be used to form new tests that are much more specific.”

CRISPR Mechanism

In all, it will likely be at least another year before clinical trials using these cell lines are completed.

Science has covered the history of Crispr, which uses a biological mechanism to activate or inhibit certain genes. One of the methods to change the genes used in the current study is called the CRISPR-Cas9 system. The Cas proteins are designed to disrupt the gene that codes for certain proteins. After the Cas proteins are injected into a cell, the cell then undergoes a sort of malfunctioning process that results in both the development of the cell itself and the appearance of new genes. Scientists can then be able to investigate how that damage was caused, or when and how it was allowed to develop.

As more research comes in about using Crispr for various treatments, scientists will have to figure out how to reduce the amount of time required for the treatment, Crispr’s effects on gene activity, and how long the effects can last. The use of the CRISPR for modifying stem cells for cancer treatment is relatively new, which makes it difficult for scientists to understand how well it works. Scientists don’t have any data on how effective it is at treating cancer, so there’s not as much concern about the potential for it to cause cancer.

Conclusion

Crispr’s use as a therapy for humans is a complicated issue, because it requires many changes that could potentially be harmful to the body. There’s a need to prove how it works and how long it takes for the changes to take place. Researchers will have to understand why it’s safe for humans to use this technology.

It’s possible that the method of using Crispr as a therapy for cancer could eventually become more mainstream, given its success in human cells in the lab. There’s a need for a regulatory framework that will allow scientists to safely use Crispr for various types of medical treatments.

How about you? Do you think that Crispr could one day be used to treat cancer? Share your opinion in comments below…

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