Achieving successful delivery of nucleic acids to skin: 6th Annual Meeting of the International Pachyonychia Congenita Consortium.

The 2009 Annual Meeting of the International Pachyonychia Congenita Consortium (IPCC)* centered on the need to develop patient-friendly technologies to effectively and efficiently deliver nucleic acids to skin. The IPCC is a group of physicians and scientists who have agreed to work together to develop therapeutics for the rare skin disorder pachyonychia congenita (PC) (a list of IPCC members can be found at http://www.pachyonychia.org). Each year’s IPCC meeting is devoted to the most pressing issues related to developing PC therapeutics and to identifying future directions toward achieving realistic goals. The consortium fully recognizes and expects that research success in this realm will be of immediate benefit not only to patients with PC but also to those suffering from other skin disorders. The 2009 meeting addressed the difficulty of delivering nucleic acids to skin. The impetus for this topic was the recent phase Ib pachyonychia congenita clinical trial using a mutation-specific small interfering RNA (siRNA), TD101. The side-by-side, dose-escalation toxicity trial of intralesional injections of this mutation-specific siRNA exhibited no toxicity at the higher doses, and a clear clinical response was observed in the siRNA-treated site, but not in the site injected with vehicle alone (Leachman et al., submitted). Unfortunately, pain from the injections was intolerable, and a decision was made that better delivery options were needed before further trials were pursued. The meeting was divided into four areas: (i) a historical overview highlighting the need for nucleic acid skin delivery, (ii) delivery technologies used in recent clinical trials, (iii) delivery technologies currently under development, and (iv) future directions in the development of nucleic acid skin delivery technologies that will be acceptable and effective.