Gene therapy for cystic fibrosis: Challenges and prospects.

Cystic fibrosis (CF) is a life-threatening autosomal-recessive disease caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CF effects multiple organs, and lung disease is the primary cause of mortality. The median age at death from CF is in the early forties. CF was one of the first diseases to be considered for gene therapy, and efforts focused on treating CF lung disease began shortly after the CFTR gene was identified in 1989. However, despite the quickly established proof-of-concept for CFTR gene transfer in vitro and in clinical trials in 1990s, to date, 36 CF gene therapy clinical trials involving ∼600 patients with CF have yet to achieve their desired outcomes. The long journey to pursue gene therapy as a cure for CF encountered more difficulties than originally anticipated, but immense progress has been made in the past decade in the developments of next generation airway transduction viral vectors and CF animal models that reproduced human CF disease phenotypes. In this review, we look back at the history for the lessons learned from previous clinical trials and summarize the recent advances in the research for CF gene therapy, including the emerging CRISPR-based gene editing strategies. We also discuss the airway transduction vectors, large animal CF models, the complexity of CF pathogenesis and heterogeneity of CFTR expression in airway epithelium, which are the major challenges to the implementation of a successful CF gene therapy, and highlight the future opportunities and prospects.

Highly Efficient and Air Stable Inverted Polymer Solar Cells Using LiF-Modified ITO Cathode and MoO3/AgAl Alloy Anode.

The performance and air stability of inverted polymer solar cells (PSCs) were greatly improved using a combination of LiF-modified ITO cathode and a MoO3/AgAl alloy anode. The power conversion efficiency (PCE) of PSCs with AgAl contact reached 9.4%, which is higher than that of the cells with Ag (8.8%) and Al electrode (7.6%). The PCE of AgAl-based PSCs can further increase up to 10.3% through incorporating an ultrathin LiF-modified ITO. AgAl-based cells also exhibit a superior stability compared to the cells with Ag and Al contacts. PCE of the AgAl-based cells without encapsulation remains 78% of its original value after the cells were aged for 380 days in air. The presence of a LiF-modified ZnO interlayer between ITO and the organic active layer improves the charge collection. The improvement in PCE and stability of the AgAl-based cells is primarily attributed to the formation of AlOx at the MoO3/AgAl interface, preventing Ag diffusion and improving the built-in potential across the active layer in the cells.