Prenatal gene therapy using adeno-associated virus serotyp-9 vectors in SMA mice

Intrauterine (IU) correction of SMN gene expression seems can be critical in the treatment of SMA disease. In this study, using Intracerebroventricular (ICV) delivery of rAAV9-SMN into mice embryos correction of disease related symptoms was investigated. For gene therapy study, 44 and 39 SMA fetuses received 4 x 10^10 vgc ss and scAAV9-SMN via ICV injection, respectively. The SMN protein expression, survival rate, and improving disease symptoms of injected mice was investigated after birth. The survival rate of IU injected SMA fetuses was around 43.85% that was lower than total survival rate (69.41%). Prenatally delivery of both ss and scAAV9-SMN vectors cause to increased lifespan of injected SMA fetuses, respectively, 63±30 ve 105±50 days. The muscle pathology and number of the motor neurons have been improved in both study groups, however, the efficiency of the scAAV9-SMN vector was determined more than ss-vector. Thus, intrauterine administration of rAAV9-SMN via ICV injection may provide a new therapeutic approach for treating SMA disease. However, further analysis should be done for investigating the safety of this method for mother and embryo.