Destination Penis? Gene Therapy as a Possible Treatment for Erectile Dysfunction

Erectile Dysfunction (ED) is a common health condition occuring in roughly 50% of aging males (40-70 years old). Recent attention has related gene therapy to ED, and now there is an interest to further implement gene therapy concepts to ED treatment. This review is an attempt to analyze key challenges and emphasize primary areas, including mostly preclinical and a few clinical trials, cellular target(s), and different viral vectors/nanoparticles for gene delivery in ED. While overexpression of target genes can be silenced by RNA interference (RNAi), down-regulation of these mechanisms has been implicated in ED. Although many patients with ED demonstrate efficacy with phosphodiesterase type 5 inhibitors, this therapy is insufficient in approximately 30-40% of patients. Although several preclinical studies for ED treatment provided promising results, gene therapy has not shown success in clinical practice, due in part to technical limitations of gene therapy to address ED pathogenesis. Developments in small RNA, such as small interfering RNA (siRNA) may lead to significant benefit in the management of ED. Also, siRNA delivery into the corpus cavernosum seems a challenging issue and awaits further development. Several safety concerns of gene therapy, gene acquisition, preparation, and delivery are necessary to continue investigation before any widespread application is used in ED treatment.