The researchers selected a gene in stem cells that they silenced, then made those stem cells into neurons or neurons. When they looked at the same gene in neurons, they found that it was still turned off in 90% of the cells. This indicates that cells retain memory of epigenetic changes even when they change cell types.
They also chose a gene to use as an example of how to use CRISPRF in treatments: the gene that codes for the tau protein, which is common in nerve cells and implicated in Alzheimer’s disease.
After testing their method in neurons, they were able to demonstrate that CRISPRoff can be used to reduce the expression of the tau protein, but the method cannot eliminate the gene completely. “What we have shown is that this is a viable strategy to block the tau and prevent expression of the protein,” Weizmann said. “The question now is: How do you manage this for an adult? Will it really be enough to affect Alzheimer’s? These are big open questions, especially the last.”
Even if the CRISPRoff technology does not lead to new treatments for Alzheimer’s disease, there are many other conditions that this technology can be applied to. And although delivery to specific tissues remains a challenge for genetics technologies like CRISPRoff, “We have shown that you can temporarily deliver it like DNA or RNA, using the same technology that supports the Corona vaccines from Moderna and BioNTech,” Weissman said.
Researchers are also excited about CFRISPRoff’s potential for research. “Since we can now close whatever part of the genome we want, it is a great tool for investigating genome function,” Weizmann said.
Additionally, a reliable system for modifying a cell’s epigenetic inheritance could help researchers discover the mechanisms by which epigenetic changes are passed on through cell divisions. “I think our tool will really allow us to start studying the mechanisms of genetics, especially epigenetics, which is a huge unanswered question in the biomedical sciences,” said Nunez.
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