Hyperactive Sleeping Beauty Transposase Enables Persistent Phenotypic Correction in Mice and a Canine Model for Hemophilia B

Sleeping Beauty (SB) transposase enables somatic integration of exogenous DNA in mammalian cells, but potency as a gene transfer vector especially in large mammals has been lacking. Herein, we show that hyperactive transposase system delivered by high-capacity adenoviral vectors (HC-AdVs) can result in somatic integration of a canine factor IX (cFIX) expression-cassette in canine liver, facilitating stabilized transgene expression and persistent haemostatic correction of canine hemophilia B with negligible toxicity. We observed stabilized cFIX expression levels during rapid cell cycling in mice and phenotypic correction of the bleeding diathesis in hemophilia B dogs for up to 960 days. In contrast, systemic administration of an inactive transposase system resulted in rapid loss of transgene expression and transient phenotypic correction. Notably, in dogs a higher viral dose of the active SB transposase system resulted into transient phenotypic correction accompanied by transient increase of liver enzymes. Molecular analysis of liver samples revealed SB-mediated integration and provide evidence that transgene expression was derived mainly from integrated vector forms. Demonstrating that a viral vector system can deliver clinically relevant levels of a therapeutic protein in a large animal model of human disease paves a new path toward the possible cure of genetic diseases

Coded Bidirectional Relaying in Wireless Networks

Abstract The communication strategies for coded bidirectional (two–way) relaying emerge as a result of successful amalgamation of the recent ideas from network coding and the broadcast/interfering nature of the wireless communication medium. In this chapter we consider the basic scenario in which two terminal nodes carry out a two–way communication, helped by a third, relay node. Insights are provided into several important ideas that arise in this simple communication scenario. The communication mechanisms can be divided into two groups, depending whether the relay node is or is not required to decode the messages from the terminals. For the class of techniques in which the relay denoises rather than decodes the messages from the terminals, we discuss the role of structured codes in achieving the highest aggregate rates in the system. The treatment of the topics is generally in an information–theoretic setting, but we also present the design of communication mechanisms when finite–length packets and practical modulation constellations are used.