Nonviral ocular gene therapy: assessment and future directions.

For multiple reasons, the eye is an excellent organ for gene therapy and while nonviral gene therapy modalities have been known for quite some time, they have only been applied to the eye in the past decade. Despite significant advances in the therapeutic effectiveness of nonviral ocular gene therapy in this time period, the clinical utility of many strategies remains questionable. Therefore, in addition to a brief summary of the status of ocular gene therapy, this review focuses on exciting current developments in non-ocular nonviral gene therapy and their application to the eye. Of specific interest are three approaches that may help to overcome the common limitations of transience in transgene expression and include the use of: (i) integrating vector systems, such as the Sleeping Beauty transposon-transposase system and the phiC31 integrase system; (ii) minicircle DNA to minimize prokaryotic vector-based silencing; and (iii) episomal replicating vectors containing chromosomal elements.