 The CRISPR-Cas9 genome editing system has revolutionized biomedical science, providing a fast and easy way to modify genes. The version of the technique that allows for the most precise edits, though, doesn't work in cells that are no longer dividing. Since that includes most of the neurons in the brain, this has limited the technology for neuroscientists. But now, a group at the Moxplunk Florida Institute for Neuroscience has figured out a way to make CRISPR work in these cells, opening up new possibilities for the field. CRISPR-based editing uses a guide RNA to direct the Cas9 endonuclease to a specific spot in the genome and make a cut in the DNA. Cellular repair mechanisms then kick into action, either in the form of non-homologous end-joining, which causes unpredictable insertions or deletions, or with homology-directed repair, which uses a donor template to make a precise change. Unfortunately, because homology-directed repair has been thought to only happen in the S and G2 phases of the cell cycle, this more desirable method does not work in post-mitotic cells, such as neurons in the brain. To overcome this problem, neuroscientists added adeno-associated virus, or AAV, to the mix. This virus can effectively provide the donor template necessary for homology-directed repair. Therefore, it seems to increase gene targeting. The team tested the approach in mouse brain slices, using CRISPR to add HA or GFP to a protein found in neurons. The gene editing beautifully lit up neurons, many of which were no longer dividing, in genetically engineered mice expressing the Cas9 protein, but the success rate depended on the dose of the virus. To more carefully study this phenomenon, the scientists set up cultures of mitotic and post-mitotic hippocampal cells, and found that post-mitotic cells need about 100 times more virus to get CRISPR to work. The group then created a dual-viral system, so they could use the technology in many animals that have not been engineered to express Cas9. This worked in both rat and mouse brain slices. Finally, the team tested the dual-viral system in living mice, including an aged Alzheimer's disease mouse model by directly injecting AAVs into the brain. The new method, which the team calls V-slender, is capable of working in virtually any brain area, cell type, and age, regardless of whether cell division is still happening, greatly expanding the types of experiments neuroscientists can do to probe the function of the brain.