Biomedical Engineering Reference
In-Depth Information
siRNAs are so called due to their silencing and TLR-activating
abilities, which may be beneficial for viral and cancer therapy
(Fig. 9.5). However, the danger upon delivery of bi-functional siRNAs
is global or systemic immune activation, perturbing the normal
physiology of the host and potentially causing damaging side effects.
Therefore, local delivery, and thus activation at the diseased cell or
tissue site, would provide the benefits of immune activation without
global immune upregulation.
9.7
siRNA-Induced Immunostimulation
Promotes Anti-tumoural Activity
in vivo
To investigate the potential benefits of bi-functional RNAi in the
treatment of HPV-driven tumours
, we developed a range of
unmodified siRNAs targeting the HPV type 16 E6/E7 oncogenes
[78]. In this study, we characterized the anti-tumour effects of non-
modified siRNAs that can target the specific HPV 16 E6/E7 oncogenes
and/or recruit the innate immune system against these HPV-driven
tumours. Firstly, these siRNAs were evaluated for gene silencing
and immunostimulatory potential
in vivo
upon system delivery of
siRNa in our stealth liposomes. We observed that our bi-functional
siRNA (IDT4) induced both IL-6 and IFN
in vivo
in the serum of mice at 8 h
compared to a non-stimulating siRNA (IDT12) or controls (Fig. 9.6).
γ
Figure 9.6
C57BL/6 mice were injected with 40 μg siRNA/mouse i.v. and
blood collected at 8 h after i.v. Serum from blood was used
in detection of pro-inflammatory cytokines in mouse CBA
inflammation kit and data read on the FACS Array. Error bar
represents ±SEM with
n
= 6.
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