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Science Papers Present GWAS of Brain Structure, System for Controlled Gene Transfer

A genome-wide association study of diffusion MRI brain scan data from nearly 44,000 individuals is published in Science this week, revealing common genetic variants that influence white matter microstructure and points to their role in a variety of conditions and diseases. White matter is critical for organizing distributed neural networks and enabling communication across brain regions. To investigate the role of genetics in white matter, a team led by scientists from the University of North Carolina at Chapel Hill performed a GWAS study and found 109 loci associated with white matter microstructure. A number of loci co-localized with brain diseases including glioma and stroke and genetic correlations are seen with white matter microstructure and 57 complex traits and diseases such as cognitive functions, cardiovascular risk factors, and various neurological and psychiatric diseases. The study, its authors write, "advances the understanding of the genetic architecture of white matter and its genetic links to a wide spectrum of clinical outcomes."

A new system for controlled gene transfer at single-cell resolution using adeno-associated viral (AAV) vectors is reported in Science Advances this week. While the precise delivery of genetic information into target cells is vital for genetic engineering research, current methods for gene transfer into specific or single cells is limited by low throughput, complicated equipment, invasiveness, or off-target effects. To address this, University of Freiburg researchers created an AAV vector system that transfers genetic information into native target cells upon illumination with cell-compatible red light. Called OptoAAV, the approach is based on a genetically modified AAV vector modified and a light-responsive adapter protein that mediates selective interaction with a target cell. They show the system can enable adjustable and spatially resolved gene transfer down to single-cell resolution and is compatible with different cell lines and primary cells. Sequential application of multiple OptoAAVs also allows for spatially resolved transduction with different transgenes, and the modular nature of the system may allow it to serve as a blueprint for rendering further classes of viral vectors light-responsive, the scientists write.