Enrico Maria Surace

Delivery of Adeno-Associated Virus Vectors to the Fetal Retina: Impact of Viral Capsid Proteins on Retinal Neuronal Progenitor Transduction

ABSTRACT The development of fetal ocular gene transfer may be useful as a therapeutic tool for the prevention of retinal genetic disorders with congenital or early clinical manifestations. In this study we explored the neural progenitor transduction patterns of adeno-associated virus (AAV) vectors following delivery to the developing retina. Recombinant vectors with the same genome carrying the enhanced green fluorescent protein (EGFP) transgene packaged in capsids of differing serotypes (serotypes 1, 2, and 5, termed AAV2/1, AAV2/2, and AAV2/5, respectively) were created. Delivery of the AAV vectors during early retinal development resulted in efficient and stable transduction of retinal progenitors. Vector surface proteins and the developmental status of the retina profoundly affected viral tropism and transgene distribution. The procedure is not detrimental to retinal development and function and therefore provides a safe delivery vehicle for potential therapeutic applications and a means of assessing the mechanisms of retina development and disease.

Phenotypic rescue after adeno-associated virus-mediated delivery of 4-sulfatase to the retinal pigment epithelium of feline mucopolysaccharidosis VI.

Mucopolysaccharidosis VI (MPS VI), due to recessively inherited 4‐sulfatase (4S) deficiency, results in lysosomal storage of dermatan sulfate in numerous tissues. Retinal involvement is limited to the retinal pigment epithelium (RPE). This study aimed to determine whether recombinant adeno‐associated virus (AAV)‐mediated delivery of 4S would reverse the RPE pathology seen in MPS VI cats.

Müller Cell Transduction by AAV2 in Normal and Degenerative Retinas

Gene therapy for retinal diseases has gained increasing attention in recent years (see review, Bennett and Maguire, 2000). Among various gene delivery systems, viral vectors such as adenovirus (Ad), adeno-associated virus (AAV) and lentivirus appear to be the most efficient vehicles for gene transfer. In comparison to the Ad and lentivirus, AAV offers several advantages, including nonpathogenicity, minimal immuogenicity, and stable transgene expression in a wide host range (Flotte and Carter, 1995; Bennett et al., 1999; Anand et al., 2000