Syn-FLEX-GCaMP6s AAV (Serotype 9)

Ideally, vectors for central nervous system (CNS) gene delivery should have the following characteristics: i) efficient transduction without off-target effects; ii) appropriate transgene expression levels and duration to induce therapeutic effects without cytotoxicity; iii) non-pathogenicity and immunogenicity without adverse reactions to treatment; iv) large-scale efficient vector production with high purity. Many AAV properties meet these requirements, which explains why this vector system is currently the most used in CNS preclinical and clinical studies.

In fact, AAV can transduce both mitotic and post-mitotic cells. In addition, most AAV serotypes have neuronal tropism, while some serotypes can also transduce other CNS cell types, such as astrocytes. Another advantage of this system is that the transgene can be stably expressed in non-human primates for the entire life span of mice and for at least 10 years in the human brain. This sustained gene expression in non-dividing cells explains why rAAV is so suitable for gene therapy of CNS diseases, which are mostly chronic and affect post-mitotic cells. In summary, AAV vectors offer the opportunity to permanently correct the disease with a single administration. Moreover, since AAV is non-pathogenic, no significant adverse effects are observed, resulting in attenuated inflammation and immune responses. In addition, rAAV cell infection results mainly in episomal transgene expression, which reduces the risk of insertional mutagenesis, an important safety concern for integrating viral vectors such as lentiviruses.