Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives

Recombinant AAV-mediated gene delivery to the central nervous system.

Various regions of the brain have been successfully transduced by recombinant adeno-associated virus (rAAV) vectors with no detected toxicity. When using the cytomegalovirus immediate early (CMV) promoter, a gradual decline in the number of transduced cells has been described. In contrast, the use of cellular promoters such as the neuron-specific enolase promoter or hybrid promoters such as the...

Measuring immune responses to recombinant AAV gene transfer.

Following AAV-based gene transfer, the occurrence of adaptive immune responses specific to the vector or the transgene product is a major roadblock to successful clinical translation. These responses include antibodies against the AAV capsid, which can be neutralizing and therefore prevent the ability to repeatedly administer the vector, and CD8(+) cytotoxic T lymphocytes, which can eliminate t...

AAV Mediated β-Thalassemia Gene Therapy

In utero AAV-mediated gene transfer to rabbit pulmonary epithelium.

In utero intra-amniotic administration of adeno-associated virus (AAV) for treatment of cystic fibrosis (CF) has the potential to be an efficient way to target the rapidly dividing undifferentiated cells of the fetal pulmonary epithelium, while simultaneously treating other tissues involved in CF (such as the intestines), but has never before been studied. Intra-amniotic administration of 1x10(...

AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy

Usher syndrome type III (USH3A) is an autosomal recessive disorder caused by mutations in clarin-1 (CLRN1) gene, leading to progressive retinal degeneration and sensorineural deafness. Efforts to develop therapies for preventing photoreceptor cell loss are hampered by the lack of a retinal phenotype in the existing USH3 mouse models and by conflicting reports regarding the endogenous retinal lo...