CAG-FLEX-NES-jRGECO1b AAV (Serotype 9)

Owing to their numerous favorable properties, AAV vectors are the platform of choice for central nervous system (CNS) gene therapy. In addition to all available serotypes and routes of administration, systemic AAV9 administration is considered a very promising approach for clinical applications. Indeed, it provides CNS-wide transgene expression through a simple and minimally invasive procedure. This is possible because AAV9 is able to cross the blood-brain barrier (BBB), which has been demonstrated in rodents, cats, dogs, and nonhuman primates.

Based on previous studies, the best candidates for this therapy are diseases characterized by: i) involvement of spinal motor neurons, ii) glial dysfunction and iii) early-onset neuronal pathology in the brain. Neonatal AAV9 administration may be an advantageous option for easily diagnosed diseases because children have lower NAbs than adults and fewer viral particles are needed for early intervention. On the other hand, treatment in adulthood may require optimized approaches to enhance neuronal transduction. In conclusion, AAV-mediated gene therapy has recently achieved some remarkable results in clinical trials. With the introduction of vascular infusion of AAV9, gene delivery has been broadly expanded into the central nervous system, a technological leap that has raised expectations for further success in gene therapy for neurological diseases.