Gene therapy for erectile dysfunction: where is it going?

This review will summarize the most recent preclinical data from the leading US laboratories regarding the application of gene therapy to the treatment of erectile dysfunction. The implications of these findings in the field of gene therapy in general, and more specifically to the treatment of non-life threatening disorders such as erectile dysfunction, will be outlined.

The preclinical work of several laboratories has clearly documented 'proof-of-concept' for the utility of gene therapy for the treatment of erectile dysfunction. A variety of vectors and several distinct molecular targets have been successfully leveraged. Such observations suggest that numerous potential strategies may exist for gene-based treatments of erectile dysfunction.

The apparent preclinical success of most, if not all, gene-based strategies for the treatment of erectile dysfunction is consistent with the multifactorial regulatory mechanisms governing the erectile process. The bottleneck in the gene therapy clinical development process therefore apparently will not lie in the ability to identify relevant molecular targets that are amenable to gene therapy for erectile dysfunction, but rather in the safety, specificity and longevity of those targets. That is, the next technical hurdle is to find the strategy(ies) that has the best safety profile, the greatest specificity for altering (increasing) intracavernous pressure 'on demand' and, furthermore, the most appropriate (longest?) half-life. While these criteria may correspond to intuition, finding molecular targets that clear these clinical hurdles may place restrictions on the molecular choices for gene transfer.