Volume 30 Issue 5, May 2023

Cover Credit: Mouse brain prefrontal cortex transduced with a mixture of AAV vectors.

The world population is aging and the prevalence of diseases affecting the nervous system is on the rise. Gene transfer with AAV vectors is a promissing “one and done” approach to target and treat disease-relevant brain areas.

To further increase the efficacy and safety of AAV-based brain gene therapies, it is important to better understand and optimize vector dosing, biodistribution and transgene expression at the single-cell level. The authors developed a simple tool to quantify with single-cell resolution, the number of incoming AAV genomes co-expressed in vivo in the mouse brain. The image shows brain prefrontal cortex co-transduced with a mixture of three AAV vectors expressing different fluorescent reporter proteins in green, blue and red. Neurons are labelled in purple, and when all three vectors transduce the same cell and co-express their genomes, neurons are labelled in white.