Toward Personalized Gene Therapy: Characterizing the Host Genetic Control of Lentiviral-Vector-Mediated Hepatic Gene Delivery

The success of lentiviral vectors in curing fatal genetic and acquired diseases has opened a new era in human gene therapy. However, variability in the efficacy and safety of this therapeutic approach has been reported in human patients. Consequently, lentiviral-vector-based gene therapy is limited to incurable human diseases, with little understanding of the underlying causes of adverse effects and poor efficacy. To assess the role that host genetic variation has on efficacy of gene therapy, we characterized lentiviral-vector gene therapy within a set of 12 collaborative cross mouse strains. Lentiviral vectors carrying the firefly luciferase cDNA under the control of a liver-specific promoter were administered to female mice, with total-body and hepatic luciferase expression periodically monitored through 41 weeks post-vector administration. Vector copy number per diploid genome in mouse liver and spleen was determined at the end of this study. We identified major strain-specific contributions to overall success of transduction, vector biodistribution, maximum luciferase expression, and the kinetics of luciferase expression throughout the study. Our results highlight the importance of genetic variation on gene-therapeutic efficacy; provide new models with which to more rigorously assess gene therapy approaches; and suggest that redesigning preclinical studies of gene-therapy methodologies might be appropriate

Green supply chain performance measurement using fuzzy ANP-based balanced scorecard:a collaborative decision-making approach

The purpose of this paper is to delineate a green supply chain (GSC) performance measurement framework using an intra-organisational collaborative decision-making (CDM) approach. A fuzzy analytic network process (ANP)-based green-balanced scorecard (GrBSc) has been used within the CDM approach to assist in arriving at a consistent, accurate and timely data flow across all cross-functional areas of a business. A green causal relationship is established and linked to the fuzzy ANP approach. The causal relationship involves organisational commitment, eco-design, GSC process, social performance and sustainable performance constructs. Sub-constructs and sub-sub-constructs are also identified and linked to the causal relationship to form a network. The fuzzy ANP approach suitably handles the vagueness of the linguistics information of the CDM approach. The CDM approach is implemented in a UK-based carpet-manufacturing firm. The performance measurement approach, in addition to the traditional financial performance and accounting measures, aids in firms decision-making with regard to the overall organisational goals. The implemented approach assists the firm in identifying further requirements of the collaborative data across the supply-cain and information about customers and markets. Overall, the CDM-based GrBSc approach assists managers in deciding if the suppliers performances meet the industry and environment standards with effective human resource