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The CRISPR Gene Editing Technique’s Latest Iteration: Base Editing

Jacob David by Jacob David
November 1, 2021
in Technology
The CRISPR Gene Editing Technique’s Latest Iteration: Base Editing
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Since its inception roughly a decade ago, CRISPR gene editing has revolutionized the world of genetic research and clinical medicine. Short for “clustered regularly interspaced short palindromic repeats,” CRISPR has made genome editing incredibly fast and easy.

However, the scientists using CRISPR, like those who used gene editing tools that came before, have run into a number of frustrating technical limitations. One of the most frustrating was CRISPR’s clumsiness as a tool for modifying extremely small sections of DNA,

While CRISPR has always been an extremely proficient way to make larger genomic modifications, it typically failed when it came to removing and/or replacing links in the DNA chain that contain just a few nucleotide base units. Is it fair to quibble about this impediment in light of the amazing feats that CRISPR gene editing has accomplished?

In fact, that most human genetic diseases are caused by mutations of just one nucleotide. Therefore, addressing these single nucleotide variations is absolutely essential when developing potential cures for some of the worst medical conditions that plague humankind.

This is where a recent iteration of the CRISPR technique known as “base editing” comes in. Thanks to the recent emergence of this novel technology, scientists can now make single base pair changes, opening the door to a whole new world of potentially life-saving clinical applications.

CRISPR researcher Maarten Geurts of the Netherlands’ Hubrecht Institute spoke about this exciting development in a recent edition of The International Journal of Life Science Methods. “With the traditional form of CRISPR, a certain piece of DNA is cut away, after which the cell has to repair itself, hopefully by replacing it with a ‘good’ piece of DNA that is made in the lab and presented to the cell,” he explained. “With the new form of CRISPR, called base editing, the mistake in the DNA is identified, but not cut and replaced; it is repaired on-site.”

In short, the increased precision of base editing allows scientists to target single base pair variations, generate appropriate gene knockouts, and correct clear-cut mutations without affecting the healthy DNA on either side. By directly converting one base pair to another, base editing can address single-nucleotide errors without cutting through the DNA itself. Prior to the development of base editing, the replacement of a single mutated nucleotide required the introduction of multiple double-strand breaks.

Contacted by Labiotech clinical writer Larissa Warneck, Jonathan Frampton, Corporate Development Partner at Horizon Discovery, explained the problems that go hand in hand with severing DNA. Specifically, this traditional CRISPR gene editing approach greatly increases the risk of mistakes in the natural intrinsic DNA repair systems of edited cells. These unwelcome changes can all too easily precipitate cellular transformations that result in cancer.

Because base editing eliminates the need to introduce double-strand breaks in the DNA chain, it makes CRISPR gene editing far safer. In fact, the dramatically smaller genomic alterations that base editing engenders have already yielded some extremely promising results in the field of cystic fibrosis research.

Cystic fibrosis arises when either a premature stop codon or the deletion of three nucleotides occurs in the CFTR gene, resulting in a non-functional protein. Although cystic fibrosis patients with the deletion mutation can be treated with medication, there is no widely accepted treatment for those with a premature stop codon.

However, base editing offers these patients new hope. Maarten Geurts and his Hubrecht Institute colleagues have used base editing techniques to cure cystic fibrosis in intestinal organoids harvested from living patients. They are now completing tests to determine if they can apply this treatment in stem cells for introduction into human patients.

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