Team uses AlphaFold AI to redesign gene-editing proteins to make them safer
A couple of decades after the discovery of systems that could selectively target DNA, we're starting to see the first therapies based on gene editing. One challenge these developments have faced is safety. While we can make them pretty specific to the gene we want edited, the human genome is very large, and even rare DNA sequences can appear a couple of times by chance. As a result, all the original gene-editing systems had known rates of what are called off-target effects, in which they simply
Get smart on it
Gene-editing systems can accidentally edit the wrong DNA sequences, a problem called off-target effects that becomes inevitable when therapies must edit many cells. Researchers used AlphaFold, an AI protein-folding software, to identify which parts of the Cas9 protein enable these mistakes by comparing protein structures when the system interacts with intended versus unintended DNA targets. By analyzing how amino acids within Cas9 make contact with RNA sequences at both correct and incorrect editing sites, the team found patterns that could guide modifications to reduce off-target editing. This approach addresses a key safety challenge in developing gene-editing therapies.
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