Recently, researchers at Stanford University attached biological nanobodies to the CRISPR tool to enhance the practicality of the technology.

By using the fundamental concept of CRISPR’s process in repairing genes, the researchers realized they could use CRISPR to locate and replace certain genes. “What we did was attach CRISPR to nanobodies to help it perform specific actions when it reached the right spot on DNA,” says Lacramioara Bintu, an assistant professor of bioengineering at Stanford.

The group of researchers utilized this technique to transform CRISPR from a gene-editing scissors agent into a more minuscule, nano scale control agent that can “turn” particular genes on and off to start/slop the flow of a health-related protein in a cell.

This new technique could allow researchers to explore new types of therapeutic applications in epigenetics (study of how genes behave inside cells).

Despite every cell in a person’s body having the same DNA, not every gene is switched on in every cell. Some cells have certain genes on, which order the cell to produce a certain protein. Other cells have disabled genes. However, the newly discovered tool is able to treat these errors.

Because CRISPR itself cannot disable genes in a controlled manner without harming the DNA, this novel tool is more convoluted; therefore, the CRISPR needs to receive assist from other larger, more complex proteins (also known as “effectors”). Therefore, when applied, the effectors can effectively select the genes and disable them.

“But these effector molecules are usually too big to easily deliver into a cell for therapeutic use,” says PhD student Mike Van, first author of the paper. To control specific cell behavior, numerous effectors may be combined together to achieve the desired effect. However, this enlarges the CRISPR-effectors combination, which hinders the process by making it harder to produce and deliver.

So, Bintu and her team utilized smaller proteins, also known as nanobodies. As nanobodies help trap the needed effectors that are swimming about within the cell like a hook, it is much more effective at targeting the specific gene.

This novel approach could be utilized to help improve epigenetic defects without having to combine CRISPR with large effectors since the cells themselves already have the needed proteins, so the researchers used nanobodies instead.

Currently, the technology is not fully verified, as team has to soon sort through millions of potential nanobodies and figure out how to bind them to CRISPR to be able to target epigenetic breakdowns.

“We just came up with a method of testing hundreds of thousands at a time,” says Bintu, who hopes to further develop the technique in future experiments.”

Fantastic Voyage: Nanobodies could Help CRISPR turn genes on and off. Stanford School of Engineering. (2021, March 3). https://engineering.stanford.edu/magazine/article/fantastic-voyage-nanobodies-could-help-crispr-turn-genes-and.

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Personal Opinion:

Honestly, as a person who has now conducted two CRISPR experiments, I definitely think that this novel technology is going to be revolutionary, considering how people are already praising CRISPR itself for being a revolutionary technology. But if we have something that is more precise and even more effective than CRISPR, than I’m really surprised.

Since CRISPR is also quite specific in its target – through Cas9 binding with the gRNA that guides the Cas9 protein, I’m fascinated how the research team wanted to make something that was even MORE specific than the Cas9 binding to a targeted sequence.

– Joanna Kim, July 30th, 2021, 1:07AM KST –