Reversible Gene Editing

The gene-editing system, CRISPR-Cas9, is truly revolutionizing medicine: in the future, it may help us eradicate ailments from sickle cell, cancer, and even blindness. While this system allows scientists to make changes to DNA, the changes are permanent. On the one hand, this is useful, because it could potentially cure genetic diseases without requiring a lifetime of treatment. The downside is that unintended consequences of the edits are difficult to fix — especially “off-targetedits, where CRISPR changes the wrong stretch of DNA. This is a huge concern for the scientific community — no one wants to be responsible for genetic mutations that go awry.

But what if the changes were not permanent? What if we could simply turn CRISPR off whenever we wanted?  A team of researchers at MIT and UCSF has developed a new gene-editing system that they call “CRISPRoff.” According to the researchers, this system can change how specific genes behave, much like CRISPR, while leaving the DNA strand unaltered — and even better, these modifications are completely reversible.

The traditional CRISPR system invented in 2012 relies on a protein called Cas9, which is found in bacterial immune systems. Cas9 can target specific genes and cut the DNA strand, removing or replacing defective genes. The DNA then self-repairs and continues functioning after the gene has been removed. Because this system alters the DNA sequence, the changes are permanent, and even though CRISPR is one of the most accurate ways to change DNA, it can be difficult to ensure that the modification will always be limited to that one gene.

As beautiful as CRISPR-Cas9 is, it hands off the repair to natural cellular processes, which are complex and multifaceted,MIT‘s Jonathan Weissman and coauthor of the study, said in a press release. “It’s very hard to control the outcomes.”

CRISPRoff is a new kind of gene-editing technology that doesn’t modify the DNA sequence, but instead changes the way those sequences are read. With this system, scientists can silence or activate various genes by adding chemical tags onto the DNA strand, without making any permanent changes. The tags cause the DNA to become unreadable by the cell’s messenger RNA, the molecule responsible for carrying instructions from the DNA to make proteins.