New Gene Editing Technique May Correct DNA Mutations in Diseases like SCA, Study Shows

New Gene Editing Technique May Correct DNA Mutations in Diseases like SCA, Study Shows

Researchers have provided more evidence of the accuracy of a recently developed gene-editing technique, showing that the method precisely induces site-specific DNA alterations in the genome. The study may have implications for gene therapy for conditions such as sickle cell anemia.

The paper, “Genome-wide target specificities of CRISPR RNA-guided programmable deaminases,” was published in the journal of Nature Biotechnology.

Currently, specific alterations in the genome are possible by using the third generation of gene-editing tools. So far, the most popular is CRISPR/Cas9, which cuts out a small DNA sequence at very specific regions. At the same time,  it allows the insertion or deletion of nucleotides (basic components of DNA) into the genome.

Researchers fine-tuned the CRISPR/Cas9 technique to replace just one of the four basic DNA nucleotides: adenine (A), cytosine (C), guanine (G), and thymine (T). The new technique may correct single-nucleotide errors in DNA, known as point mutations.

Importantly, gene-editing tools have a probability of inducing mutations in nucleotide sequences that are very similar to the target gene sequence. They’re called off-target mutations.

In this study, researchers developed an informatics tool to assess the accuracy of single-nucleotide editing. They improved an existing computer program (Digenome 2.0) to identify off-targets in the entire genome. This computer software may also help increase the specificity of the nucleotide-editing.

“It is the first time that the accuracy of this base editor has been verified at the whole genome level,” Kim Jin-Soo, the leading author of this study, said in a press release.

The team found that the base editor technique is more accurate than CRISPR-Cas9 because it induces fewer off-target DNA changes. The base editing technique induced C-to-T conversions in 1 to 67 sites in the human genome, while CRISPR/Cas9 caused cleavages in 30 to 241 sites. “Therefore, it is expected that these base editors will be used as widely as the popular CRISPR technology,” Kim Jin-Soo said.

This new technique may offer a powerful approach to treat inherited genetic diseases associated with gene point mutations, such as sickle cell anemia. These patients have one of these point mutations in the β-globin chain of hemoglobin, and could have this mutation corrected by this technique.

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Teresa F. Pais holds her PhD in Biomedical Sciences from University of Porto. She has worked in innate immune responses in the context of both infection and neurodegeneration. Currently, she is a researcher at Instituto de Medicina Molecular where she investigates inflammatory processes in the brain.

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