Recombinant adeno-associated viruses (rAAVs) have been widely used in the gene therapy field for decades. However, because of the challenge of effectively delivering rAAV vectors through the blood-brain barrier (BBB), their applications for treatment of central nervous system (CNS) diseases are quite limited. In this study, we found that several cell-penetrating peptides (CPPs) can significantly enhance the
in vitro
transduction efficiency of AAV serotype 9 (AAV9), a promising AAV vector for treatment of CNS diseases, the best of which was the LAH4 peptide. The enhancement of AAV9 transduction by LAH4 relied on binding of the AAV9 capsid to the peptide. Furthermore, we demonstrated that the LAH4 peptide increased the AAV9 transduction in the CNS
in vitro
and
in vivo
after systemic administration. Taken together, our results suggest that CPP peptides can interact directly with AAV9 and increase the ability of this AAV vector to cross the BBB, which further induces higher expression of target genes in the brain. Our study will help to improve the applications of AAV gene delivery vectors for the treatment of CNS diseases.
As the offshoring becomes more widespread, business practitioners outsource their activities to overseas countries. Although there is a wealth of academic literature examining outsourcing and offshoring, there is little academic literature that addresses the current outsourcing decision most firms facing, which is where to outsource. Given multi-attribute nature of offshore location selection, this paper argues that five factors should be considered for decisions, and proposes the use of analytic hierarchy process (AHP) and PROMETHEE as aids in making offshore location selection decisions. AHP is used to analyze the structure of the location selection problem and determine weights of the criteria, and PROMETHEE method is used for final ranking, together with changing weights for a sensitivity analysis. It shows by means of an application that the hybrid method is very well suited as a decision-making tool for the offshore location selection decision. Finally, potential issues for future research are presented.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.