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April 10, 2021 02:02 am

New, Reversible CRISPR Method Can Control Gene Expression While Leaving DNA Sequence Unchanged

fahrbot-bot shares a report from Phys.Org: Over the past decade, the CRISPR-Cas9 gene editing system has revolutionized genetic engineering, allowing scientists to make targeted changes to organisms' DNA. While the system could potentially be useful in treating a variety of diseases, CRISPR-Cas9 editing involves cutting DNA strands, leading to permanent changes to the cell's genetic material. Now, in a paper published online in Cell on April 9, researchers describe a new gene editing technology called CRISPRoff that allows researchers to control gene expression with high specificity while leaving the sequence of the DNA unchanged. The classic CRISPR-Cas9 system uses a DNA-cutting protein called Cas9 found in bacterial immune systems. The system can be targeted to specific genes in human cells using a single guide RNA, where the Cas9 proteins create tiny breaks in the DNA strand. Then the cell's existing repair machinery patches up the holes. Because these methods alter the underlying DNA sequence, they are permanent. That's where the researchers saw an opportunity for a different kind of gene editor -- one that didn't alter the DNA sequences themselves, but changed the way they were read in the cell. This sort of modification is what scientists call 'epigenetic' -- genes may be silenced or activated based on chemical changes to the DNA strand. Epigenetic gene silencing often works through methylation -- the addition of chemical tags to to certain places in the DNA strand -- which causes the DNA to become inaccessible to RNA polymerase, the enzyme which reads the genetic information in the DNA sequence into messenger RNA transcripts, which can ultimately be the blueprints for proteins. With this new CRISPRoff technology, one can [express a protein briefly] to write a program that's remembered and carried out indefinitely by the cell.

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