during the freezing step, and sugars have a limited capacity to protect against freezing-induced damage (28). Furthermore, industrially, the freeze-drying (lyophiliza- tion) process is known to be much more cumbersome and costly than the conventional heat-based pharmaceut- ical drying procedure. Additionally, it was shown that the lyophilized lipoplexes suffered progressive loss in transfecetion efﬁciency when subjected to stability settings similar to what we have used in the present study (27). The degradation was mainly due to the gener- ation of reactive-oxygen species and was increased in the presence of metal contaminants (27,37). Consequently, chelators were used to enhance the stability proﬁle; however, the effects of these additives on vector stability during lyophilization are difﬁcult to predict (37). To our knowledge, PF14 is the ﬁrst vector reported to retain nearly 100% of its transfection efﬁciency utilizing a heat-based drying and dispersion procedure. Furthermore, PF14 showed a very good stability proﬁle in the absence of add- itional formulation requirements. In conclusion, we have shown that the chemically modiﬁed CPP, PF14, is able to efﬁciently deliver SCOs to different cell-lines including a disease-relevant hard- to-transfect cell-line, H2K. Furthermore, we have success- fully been able to formulate PF14-SCO nanocomplexes into solid formulation utilizing the solid dispersion tech- nique using a convenient heat-based drying method. The solid formulations demonstrated splice-correction activity almost identical to the freshly prepared nanocomplexes; however, this efﬁciency was sensitive to the type of excipi- ent used and its concentration. The nanocomplexes remained intact after formulation and the formulation remained active even when subjected to stressful stability conditions for 2 months. Importantly, being able to for- mulate PF14 nanocomplexes into an active and stable solid formulation is an important proof-of-principle that CPP-based therapeutics could be incorporated in solid pharmaceutical forms. This could signiﬁcantly extend the horizon of therapeutic applications of CPPs. Collectively, our results suggest that PF14 is a promising translational approach for delivering SCOs in different pharmaceutical forms and opens new opportunities to develop more pharmaceutically relevant assays for CPPs. SUPPLEMENTARY DATA Supplementary Data are available at NAR Online. ACKNOWLEDGEMENTS We would like to thank Johanna Unger for her assistance in the preparation of the initial experiments. The confocal imaging study was performed at the Live Cell Imaging unit, Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. FUNDING Swedish Research Council (VR-NT); VINNOVA- SAMBIO joint project; SSF (Sweden-Japan); Center for Nucleic Acids Research, 2011, Vol. 39, No. 12 5297 Biomembrane Research, Stockholm; Knut and Alice Wallenberg’s Foundation; the EU trough the European Regional Development Fund through the Center of Excellence in Chemical Biology, Estonia; the targeted ﬁnancing SF0180027s08 from the Estonian Government; the DoRa Program of The European Social Fund; Archimedes Foundation; the Torsten and Ragnar So¨ derberg Foundation; KI faculty funds for funding of postgraduated students (to J.R.V.); Egyptian Ministry of Higher Education (to E.M.Z.); Swedish Society of Medical Research (SSMF to S.E.A.); Work in the Gait laboratory is supported by the Medical Research Council (Unit program U105178803). Funding for open access charge: Swedish Research Council (VR-NT). Conﬂict of interest statement. None declared. REFERENCES 1. Munos,B. (2009) Lessons from 60 years of pharmaceutical innovation. Nat. 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