The commonly used adeno-associated virus is small, and although some Cas9 proteins can enter it, Cas12a proteins are generally too large. However, researchers have identified a relatively small version of Cas12a, called EbCas12a, which occurs naturally in a species of the bacterial class Erysipelotrichia. They increased the gene-editing efficiency by deliberately replacing one of the protein’s amino acid building blocks with another. enEbCas12a has a gene-editing efficiency comparable to two other Cas12a proteins known for their precise gene-editing. The research team demonstrated that enEbCas12a is small enough for adeno-associated virus-based gene therapy. They modified enEbCas12a to target a specific gene associated with cholesterol, integrated it into the virus, and administered it to mice with high cholesterol levels. One month later, they observed a significant reduction in blood cholesterol levels in the treated mice compared with mice without the virus. Further research will be needed to determine whether enEbCas12a could one day be used to combat human disease.
