Advanced CRISPR Technology Enables Large-Scale Gene Screening in Live Mouse Brains

Recent advances in genetic research have significantly improved techniques for studying and manipulating neurophysiological processes. One such breakthrough involves a highly refined CRISPR platform that allows scientists to perform large-scale gene screening directly within live mouse brains. Developed by researchers at the University of California, San Francisco, and published in Nature Neuroscience, this novel method is called CRISPR screening by AAV episome sequencing (CrAAVe-seq).

Traditional CRISPR techniques have been invaluable for gene editing, but their application in complex tissues like the brain has been limited. These methods often face challenges such as delivery efficiency, specificity, and scalability. The new CrAAVe-seq approach overcomes these hurdles by leveraging adeno-associated virus (AAV) vectors to deliver single-guide RNAs (sgRNAs) into the brain efficiently, enabling the disruption of thousands of genes across different cell populations.

By isolating and sequencing AAV genomes from the brain tissue after some time, researchers can determine which genes are critical for specific cell types, such as neurons or astrocytes. This allows scientists to perform high-throughput, in vivo genetic screens with remarkable precision and scalability. The platform also facilitates targeting specific brain regions or cell populations, broadening its potential for neurological research.

One key innovation is pairing the sgRNA delivery with genetic tools that 'record' their presence in specific cells. This technique ensures that the gene perturbation effects can be traced back to particular cell types, making it possible to study gene functions in their natural tissue environment. The approach has demonstrated robustness even in studies involving a single mouse, showcasing its reproducibility and scalability.

This technology holds immense promise for unraveling the complex genetic networks underlying neural function and disease. Future applications could include investigating genetic factors in neurodegeneration, neuropsychiatric disorders, and brain development, paving the way for targeted therapies. As Dr. Ramani and colleagues continue to refine CrAAVe-seq, its versatility is expected to expand, offering a powerful tool for large-scale genetic and neural studies in vivo.

Source: https://medicalxpress.com/news/2025-09-precise-crispr-platform-enables-large.html