Nanobodies to help CRISPR turn genes on and off in cells

The CRISPR genetic tool has been compared to molecular scissors for its ability to cut and replace genetic code in DNA. But CRISPR has capabilities that could make it useful for tasks other than genetic repair.

In a recent study, scientists have found that CRISPR can pinpoint the location of specific genes. Biologists have attached CRISPR to nanobodies to help them perform specific actions when they reach the right place on DNA.

The new method, presented in the journal Nature Communications, will allow researchers to explore new therapeutic applications in epigenetics – studying the behavior of genes within cells.

Every cell in the human body has the same DNA – a complete set of genes, but not every gene is included in every cell. Some cells have certain genes that tell the cell to make certain proteins. For some, these genes are turned off, while for others they are turned on. Sometimes, as is the case with genetic diseases, this switch goes awry. A new tool created in the laboratory of Lacramioar Bintu, assistant professor of bioengineering at Stanford, could correct these errors.

It’s much more complicated than scissors because regular CRISPR can’t turn genes on and off in a controlled way without breaking DNA. To make changes without harming DNA, CRISPR needs the help of other large, complex effector proteins. With a new combo tool, CRISPR finds the gene you want, and the effector can flip a switch.

The problem is that these effector molecules are usually too large to be easily delivered to the cell for therapeutic use. To complicate matters further, multiple effectors are commonly used in combination to precisely regulate specific cellular behavior. This makes the combination of CRISPR effectors even larger and therefore more difficult to manufacture and deliver.

To get around this hurdle, the team turned to smaller proteins called nanobodies. Nanobodies do not replace effectors. Instead, they act as tiny hooks that catch the required effectors that are already inside the cell. All you have to do is choose the right nanobody, and it uses the right effector to switch.

The new technique can be used to correct epigenetic defects without the need to combine CRISPR with large effectors.

At the moment, the technique is at the stage of concept verification. The next step for the team will be to sort through the millions of potential nanobodies and figure out how to attach them to CRISPR to target specific epigenetic disorders.

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Alexandr Ivanov earned his Licentiate Engineer in Systems and Computer Engineering from the Free International University of Moldova. Since 2013, Alexandr has been working as a freelance web programmer.
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Alexandr Ivanov

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