Development and Validation of CRISPR Activator Systems for Overexpression of CB1 Receptors in Neurons
For several years, approaches using viral vectors have been the focus of gene therapy research against neurological disorders. These are typically limited to the delivery of single genes and often do not manipulate the expression of the endogenous locus.
In the last years the advent of CRISPR-Cas9 technologies, allowing efficient manipulation of endogenous genes, have revolutionized many areas of scientific research. Although successfully used in neurons, they have not yet been extensively applied for the overexpression of genes involved in synaptic transmission.
In this study, Ledri et.al describe the development and application of two different CRISPRa systems, and demonstrate their efficiency in expressing the Cnr1 gene, coding for neuronal CB1 receptors. Both approaches were similarly efficient in primary neuronal cultures, while one approach was more efficient in vivo.
The results show that CRISPRa techniques could be successfully used in neurons to target overexpression of genes involved in synaptic transmission, and potentially represent a next-generation gene therapy approach against neurological disorders.