Vector-borne pathogens have evolved molecular mechanisms of vector-pathogen interactions that involve genetic traits of both the vector and the pathogen [ 5, 35].
Financial support was provided by the Deutsche Forschungsgemeinschaft (SPP1230 priority program "Mechanisms of gene vector entry and persistence" and Excellence cluster ("NIM").
Financial support by the Deutsche Forschungsgemeinschaft BAA 2035/3-1 and SPP1230 priority program "Mechanisms of gene vector entry and persistence") and the Bundesministerium fuer Bildung und Forschung (BMBF BioChancePLUS/FKZ: 0315182) to AB is gratefully acknowledged.
The mechanisms of DNA vector-based approaches involve the synthesis of small RNA from a DNA template under the control of RNA polymerase III (Pol III) promoter in transfected cells.
Although there is discussion in the field as to the exact mechanism of dual vector treatments (i.e. repair vs. homologous recombination), our work with AAV5.DYSF, 16 and that of others, 29, 37, 38 points to homologous recombination of partially packaged genomes as the mechanism responsible for the generation of full-length transcripts.
In order to create such a mechanism, the theory of vector similarity is defined.
Our results establish a novel and simple way to engineer chromosomes in vivo and provide further insights into the mechanisms of recombinant AAV vector integration in vivo.
The reason by which this synergy operates or can be abolished may involve multiple mechanisms, since the type of vector, cytokine and bacteria employed in this study are able to trigger a diverse spectrum of effects and pathways [ 17, 18, 28, 42, 45] and therefore, their relative contribution will require further investigations.
Taking advantage of novel in vivo genotoxicity assays, we tested a battery of LV constructs, including some with clinically relevant designs, and found that oncogene activation by promoter insertion is the most powerful mechanism of early vector-induced oncogenesis.
Many of these association studies include mechanisms of phenotypes that affect vector capacities of these malaria mosquito species, which will create new avenues for vector control strategies.
