Biomedical Engineering Reference
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immunotherapy by targeting genes involved in immune inhibition
for cancer treatment. This concept was achieved by conjugating a
siRNA that targets the immune suppressor gene Stat3 to a CpG
oligonucleotide agonist of TLR9. This conjugation enabled three
activities in a single molecule: immune cell targeting and TLR
activation by CpG and immune checkpoint silencing by the siRNA
[77]. The study found that the combination of siRNA silencing
and CpG immune activation caused potent anti-tumour immune
responses. All of the above studies clearly identify the benefits of
siRNA silencing together with the additional benefits of immune
activation for therapeutic application.
Figure 9.5
Bi-functional RNAi targeting tumour cells. Combined benefit
of direct gene silencing from RNAi mechanism and siRNA
immune system activation targeting tumour cells.
While immune activation by siRNAs has been readily dismissed
in the majority of studies as an unwanted side effect of the silencing
agents, the above research indicates that immune stimulation may
be beneficial. An emerging concept proposed by our group aims to
utilise the ability of siRNAs themselves to activate innate immune
responses and design potent “bi-functional siRNAs”. Bi-functional
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