A new method called CloneSelect, recently described in Nature Biotechnology, offers researchers a better way to pick out individual cell clones from large and complex populations, something that’s often crucial in genetic studies, drug screening, and stem cell research.
The technique is based on CRISPR base editing and uses genetic barcodes to track and isolate specific cells. According to the researchers, CloneSelect performed better than existing approaches in isolating target clones, particularly because it avoids some of the downsides seen in older methods, like random editing errors and cell toxicity.
“CloneSelect enables the isolation of target barcoded cells from a complex population using CRISPR base editing… Compared to the other retrospective clone isolation methods tested in this study, CloneSelect demonstrated an ability to isolate cells with an overall higher performance.”
One of the more interesting aspects of CloneSelect is that it works across different types of organisms, including human stem cells, yeast, and bacteria. That makes it potentially useful in a wide range of experiments, from studying cell fate in early development to improving the efficiency of synthetic biology projects.
In tests, CloneSelect was able to isolate clones even when they made up just a tiny fraction of the population, down to one in 100,000 in some bacterial samples. However, the success rate wasn’t perfect across the board. For example, in yeast, the method had a lower success rate, which the authors suggest might be due to the way fluorescent colonies were picked.
The method doesn’t just identify the right cells, it keeps them alive, which means they can be studied further or even used in future experiments. The team suggests applications ranging from analyzing gene expression in stem cells to recovering rare products from DNA assembly reactions.
While CloneSelect isn’t a silver bullet, it looks like a solid step forward for labs trying to sift through complex cell mixtures to find exactly the right clone. The paper points out that even if the first attempt doesn’t succeed, researchers can try again using different guide RNAs, something that could make the method flexible enough for many experimental setups.