Researchers Identify New Protein to Enhance CRISPR

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Researchers from University of Texas at Austin (UTA) suggest that lesser-used CRISPR proteins, Cas12a would lead to safer and effective gene editing.

Researchers from The University of Texas at Austin identified an easy upgrade to CRISPR—a gene editing tool, by using Cas12a protein. Although Cas9 is the most popular enzyme currently used in CRISPR gene editing, it has less effectiveness and precision than one of the lesser-used CRISPR proteins, called Cas12a. Cas9 disrupts healthy functions in animals and plants as it often edits the wrong part of a plant’s or animal’s genome. CRISPR technology analyses human genes and genetically modify plants and animals however, the system often tends to target the wrong spot in a genome. Such errors could lead to emergence of new disorders in humans instead of providing a curing.

The research led by Isabel Strohkendl, a graduate student  and professor Rick Russell from UTA, found that the protein Cas12a effectively binds to a genomic target as compared to Cas9. Each enzyme carries a short string of genetic code written in RNA and starts trying to bind to the DNA by forming base pairs when it bumps into some DNA. The enzyme starts the binding at one end and works its way along as it tests match of each letter on one side (the DNA) to the adjacent letter on the other side (the RNA).

Each base pair in Cas9 sticks together tightly and when the first few letters on each side match well, it strongly bounds to the DNA. Therefore, Cas9 pays less attention as the process goes on and concentrates on the first seven or eight letters in the genomic target. It overlooks a mismatch later in the process that would lead it to edit the wrong part of the genome. The bonds in Cas12a are relatively weak at each point along the way, owing to which it takes a good match all along the strip. This enables for the two sides to hold together long enough to make an edit and result in editing only the intended part of the genome. The research was published in the journal Molecular Cell on August 2, 2018.

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