Human immunodeficiency virus type 2 (HIV-2) vector-mediated in vivo gene transfer into adult rabbit retina.

PURPOSE: To evaluate the potential usefulness of HIV-2 viral vector in in vivo retinal gene therapy.

METHODS

An HIV-2 virus based viral vector was constructed and administered subretinally and intravitreally into rabbit eyes. After viral vector administration, the eyes were closely monitored for any adverse effects by slit lamp, indirect ophthalmoscopy, and fundus photography. Eyes were enucleated at specified times after injection, and reporter gene expression was identified within cell types and graded by the pattern and distribution of staining cells using fluorescent microscopy.

RESULTS

The HIV-2 viral vector demonstrated efficient gene transfer into many types of retinal cells without apparent cytotoxicity. Notably with subretinal injection, the HIV-2 vector resulted in higher efficiency of transduction of photoreceptor cells than of the other cell types (p < 0.05). With the intravitreal administration of HIV-2 viral vectors, cellular transduction and transgene expression in the ganglion cell layer was the dominant finding.

CONCLUSIONS

HIV-2 viral vector may be a useful gene delivery vehicle for retinal photoreceptor cells and ganglion cells. It deserves further exploration to investigate its potential merit in long term gene therapy protocols and in other animal species.