Lipid-Like Delivery Materials for Efficient siRNA Delivery - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 173

tests analogous to the F7 assay might identify tissue-specific
delivery vehicles, particularly in endocrine organs. However, an ideal
assay would measure delivery to every tissue simultaneously and
inexpensively. A recently reported mouse model meets these criteria;
mice were genetically modified to express luciferase wherever
knockdown of a transcriptional repressor occurs.

61

Though spatial
resolution using whole-body bioluminescence is somewhat limited,
this assay is amenable to high-throughput studies, as the efficacy
of many delivery vehicles can be investigated in parallel without
sacrificing the mice and harvesting their organs, which is another

effective approach to assess pharmacodynamics, albeit at lower
throughput. Such improved

62

assays, and others like it, will help
uncover structure-function relationships governing the important
objective of non-liver delivery. The iterative, combinatorial approach
described herein (Fig. 7.5) represents one rigorous approach to
achieve this aim.

in vivo

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