Genome Editing Could One Day Help Treat Diseases

By Kylie Wolfe

What if scientists could unleash the potential of genome editing on diseases that affect the heart or muscles? That may soon be possible. Genome editing technologies have evolved over the last several decades, leading to faster and more accurate methods. These techniques make it possible to cut and replace sections of DNA, changing their expression.

One new approach is being explored at Rice University in Houston, Texas. Researchers in the Xue Sherry Gao laboratory found a way to correct dozens of genetic errors at once. And they think their CRISPR-based approach could help treat diseases that are triggered by mistakes in multiple genes. Their work was published in Nature Communications.

Bringing Simplicity to the Field

To create a more advanced gene editing tool, the team used drive-and-process (DAP) arrays instead of the more common CRISPR-Cas12a or CRISPR-Cas9. DAP arrays are unique because they use transfer RNA (tRNA) molecules, which typically play a key role in protein synthesis. In this case, tRNA serves as a promoter of and driver for guide RNA (gRNA) expression.

With this in mind, the team engineered a 75-nucleotide tRNA molecule capable of making DAP arrays. Those arrays were then able to complete “up to 31 edits with the base editor and three edits with the prime editor,” as mentioned in a Rice News article.

“Previously, if we wanted to edit multiple genes in the same cell, we would have to do them one after another, which is very time consuming and low efficiency,” said graduate student Qichen Yuan in the article.

When gRNAs are released at genomic sites, they can recognize regions of interest, sending editors toward specific DNA targets. This results in fewer off-target edits, making it a very effective tool.

“Since we are introducing multiple gene edits at once, one could imagine it might lead to more off-target edits,” said Xue Sherry Gao, principal investigator, in the same article. “But our experimental data is very impressive. We actually observed fewer off-target activities while maintaining the same level of on-target editing with DAP arrays.”

The new genome editing strategy could make it easier to fix errors with efficiency and precision.

Fixing Errors Efficiently

The new genome-editing strategy could make it easier to fix errors with efficiency and precision. The team tested various DAP arrays and determined that they can make disease-suppressing changes in human cells. Although some attempts were more successful than others, the gRNAs performed well and caused very few unwanted edits.

Some existing methods, like CRISPR-Cas9, can’t process gRNA in the same way, while other strategies have less success avoiding off-target changes, an advantage of the team’s new approach.

The DAP arrays may be more useful because they release the right number of gRNAs to complete the edits. They also don’t require long DNA promoter sequences to set gRNAs in motion, reaching a range of targets.

Making Advancements in New Ways

The team’s use of DAP arrays could bring simplicity to an otherwise complex field and has the potential to positively impact biology research, engineering, and disease treatment.

“We anticipate we could pair DAP arrays with base editors, prime editors, and other emerging CRISPR technologies, such as multiplex CRISPR screening and studying of polygenic diseases in vivo,” Gao said in the Rice News article. “Our lab has a current focus using these technologies for the disease modeling and treatment of cystic fibrosis.”

As more experiments get underway, scientists will continue to close in on an answer—one that may bring the power of genome editing to disease treatment.

Kylie Wolfe is a Thermo Fisher Scientific staff writer.

Genome Editing Could One Day Help Treat Diseases