AAV9-CMV-FLPo

Gene therapy strategies involve replacing defective genes with functional ones, or downregulating dysfunctional genes to block their deleterious effects. Many clinical gene therapy trials conducted to date have sought to treat monogenic diseases, which are caused by mutations in a single gene product. However, many diseases, such as diabetes, heart disease, and neurological disorders, are multifactorial in nature and would be challenging to treat using gene replacement alone. Some non-viral gene delivery methods currently in use involve electroporation of naked DNA or the use of liposome complexes, in which the DNA is protected by a liposome shell. These non-viral vectors have the advantage of being able to deliver larger genes and produce low host immunogenicity, but suffer from low transgene expression and short lifespan. The most promising gene delivery method uses viruses, which have evolved to be highly efficient at infecting specific host cell types and delivering and expressing their genomic payloads.

The most widely used viral vectors are derived from adenoviruses, retroviruses, and parvoviruses, each of which has been shown to be highly effective in gene delivery and expression. Adeno-associated virus (AAV) belongs to the parvovirus family and has demonstrated a good safety profile. The field of recombinant adeno-associated virus (AAV) gene therapy has matured since the first clinical trials for cystic fibrosis. Although AAV induces a transient increase in cytokine levels after injection into mice, studies have found that it induces minimal immunogenicity and causes little inflammation after several hours. AAV is suitable for many medical applications because it can transduce non-dividing cells in a variety of tissues or organs. AAV has become a powerful tool for therapeutic gene delivery.