Ординатура / Офтальмология / Английские материалы / Ocular Neuroprotection_Levin, Polo _2003

deleted [110,111]. By eliminating these cis-acting elements, the virus loses its capacity for gene expression directed by both LTRs, resulting in inactivation of the integrated virus in the infected cells. In addition, the expression of the transgene of interest can only be controlled by an internal heterologous promoter. A stable, high-output packaging cell line to produce this latest generation of LV vectors has been recently reported [112]. These results represent the latest advancement in the efforts to render HIV-based vectors safe for clinical use. Although these novel vectors greatly minimize the risk of RCR virus infection to users during manipulation and preparation, the biosafety of LV vectors in vivo has yet to be demonstrated.

VII. SUMMARY

Several independent research laboratories have recently established proof-of- principle for the efficacy of gene therapy for neuroprotection in animal models of retinal injury or disease. Three viral systems, Ad, AAV, and LV, have been used for most gene delivery applications to the retina both in vitro and in vivo. The pros and cons inherent in each of these vectors need to be carefully weighed when designing a gene transfer strategy. Recent progress in the methods to create these recombinant viruses has greatly increased the ability of researchers to generate high-titer and pure stocks while reducing production times. In addition, the likelihood of adverse reactions in the host tissues and the risk of RCR virus generation have been minimized. As these viral vectors progress toward preclinical and potential clinical human trials, highly stringent standards for their efficacy, biosafety, ease for scaling up production and purity will be expected. Future in vivo characterization of these viral vectors will be essential to fully assess if these requirements are met for clinical applications.

ACKNOWLEDGMENTS

Supported by the Canadian Institutes of Health Research (CIHR) and the Foundation Fighting Blindness. A.D.P. is a scholar of Fonds de la Recherche en Sante´ du Que´bec.

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