Delivery of adeno-associated virus vectors to the fetal retina: impact of viral capsid proteins on retinal neuronal progenitor transduction.
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.
Surace
Enrico M
EM
F. M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, Scheie Eye Institute, 310 Stellar Chance Building, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, PA 19104-6069, USA.
Auricchio
Alberto
A
Reich
Samuel J
SJ
Rex
Tonia
T
Glover
Ernest
E
Pineles
Stacey
S
Tang
Waixing
W
O'Connor
Erin
E
Lyubarsky
Arkady
A
Savchenko
Andrey
A
Pugh
Edward N
EN
Maguire
Albert M
AM
Wilson
James M
JM
Bennett
Jean
J
D000818:Animals; D036022:Capsid Proteins / Q000235:genetics*; D002454:Cell Differentiation; D000229:Dependovirus / Q000145:classification / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000821:virology; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000196:embryology; D011247:Pregnancy; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000821:virology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology / Q000821:virology; D014161:Transduction, Genetic; D019076:Transgenes
D036022:Capsid Proteins; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins