Syn-GFP AAV (Serotype Retrograde)

Gene therapy, in simple terms, is the rescue or correction of a disease phenotype in a patient's cells by delivering a transgene. While there are many strategies for delivering gene therapy to target tissues, AAV has emerged as the gold standard viral vector because it is safe, effective, and has broad tropism for a variety of tissues and organs. AAV is a small (~25 nm), single-stranded (ss) DNA virus consisting of a short genome (4.7 kb) encapsidated by a protein capsid. The viral genome consists of genes that direct vector replication (rep genes) and capsid structural proteins (cap genes). Importantly, AAV cannot replicate independently and requires co-infection with adenovirus (or another helper virus, such as herpes simplex virus) to replicate. AAV used for gene therapy lacks the rep and cap genes and is instead provided in trans by producer cells. This increases the safety of the vector and opens up packaging capacity for the transgene of interest.

Recombinant AAV vectors retain only the inverted terminal repeats (ITRs) of the wild-type virus. The ITRs are the only part of the wild-type AAV genome (wtAAV) required for functional packaging and transduction. A key advantage of using AAV in gene therapy is its versatility: there are dozens of naturally occurring serotypes, with more being discovered, each with distinct transduction properties. These properties can be further modified through the use of promoter and enhancer elements to transcriptionally regulate transgene expression, such as the synapsin promoter for customized neural expression.