4 research outputs found
Recommended from our members
Synthetic virology approaches to improve the safety and efficacy of oncolytic virus therapies.
The large coding potential of vaccinia virus (VV) vectors is a defining feature. However, limited regulatory switches are available to control viral replication as well as timing and dosing of transgene expression in order to facilitate safe and efficacious payload delivery. Herein, we adapt drug-controlled gene switches to enable control of virally encoded transgene expression, including systems controlled by the FDA-approved rapamycin and doxycycline. Using ribosome profiling to characterize viral promoter strength, we rationally design fusions of the operator element of different drug-inducible systems with VV promoters to produce synthetic promoters yielding robust inducible expression with undetectable baseline levels. We also generate chimeric synthetic promoters facilitating additional regulatory layers for VV-encoded synthetic transgene networks. The switches are applied to enable inducible expression of fusogenic proteins, dose-controlled delivery of toxic cytokines, and chemical regulation of VV replication. This toolbox enables the precise modulation of transgene circuitry in VV-vectored oncolytic virus design
The Binding of Religious Heroes in Andreas and the HĂȘliand
Scholarly approaches to the Old English Andreas have tended to emphasise the poem's formulaic debt to Beowulf and the works of Cynewulf, but as of yet unexplored is its strikingly similar use of the binding motif also present in the Old Saxon alliterative gospel, the HĂȘliand. These two poems, likely produced in a similar period, share not only a depiction of bound religious heroes that far outstrips their sources, but also specific formulaic and linguistic parallels. The suggestion that the HĂȘliand's preoccupation with the binding of Christ stems directly from the experience of those Saxons subjugated by the Franks is, therefore, problematised when we take into account the formulaic nature of binding terminology in the closely related language of Old English. Similarly, a desire to read the binding of the saints in Andreas as a unique innovation does not take into account the possibility that the poet may have been familiar with a tradition in which Christ's Passion includes binding. In discussing these two texts together, this paper emphasises a cross-cultural interest in bondage, as well as the importance of exploring formulaic connections between the Old English and Old Saxon corpora