Novel RNA Interference (RNAi)-Based Nanomedicines for Treating Viral Infections - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 211

E6 and E7 proteins make the corresponding RNA transcripts targets
for anti-HPV RNAi therapies. siRNAs targeting the E6 protein of HPV-
16 are capable of inhibiting expression of both E6 and E7, as both
mRNAs are bicistronically transcribed. HeLa cervical cancer cells
transduced with a lentiviral vector-expressing shRNAs targeting the
HPV-18 E6 RNA produced significantly smaller tumors in Rag -/- mice.
Tumor repression was dosage dependent with high doses of shRNA-
expressing vector completely abrogating tumor development [47].
Moreover, systemically delivered lentivirus-shRNA could inhibit the
growth of established tumors in a murine lung metastasis model.
In an interesting variation to RNAi-based tumor therapy, the RNAi
mechanism was used to induce anti-tumor immune responses to
HPV proteins. Translation of incomplete protein products from
anti-E6 shRNA-cleaved mRNA resulted in increased presentation
of the target protein and the generation of immune response that
protected mice from a subsequent challenge with tumor cells
[46]. More recently, anti-E6/E7 siRNAs designed using the current
algorithms for optimal siRNAs were very eff ective in controlling
tumor growth in a therapeutic in vivo experimental setup in NOD/
SCID mice. siHa HPV16+ cervical cancer cell-derived tumors could
be regressed as late as 6 weeks after tumor establishment by daily
intratumoral injections of anti-E6/E7 siRNA for a total of 30 days
[126]. All these promising data suggest that RNAi therapy may speed
up the reduction in rates of HPV incidence and cervical cancer when
used in parallel with HPV vaccines.

7.2.3 Herpes Simplex Virus 2 (HSV-2)

HSV-2 is a sexually transmitted viral infection, which often produces
painful sores, usually in the genital area. It has been estimated that
536 million people are infected with HSV-2 globally [82]. Suppressive
antiviral drugs like valacyclovir eff ectively minimize symptoms and
reduce the risk of viral transmission during a symptomatic outbreak.
However, the mostly asymptomatic nature of HSV-2 infections is
a huge cause for concern as HSV-2 is also an important cofactor
for transmission of the HIV. People infected with HSV-2 are twice
as likely to become infected with HIV and four times as likely to
transmit HIV to others [19]. A topical microbicide with the ability to
protect against HSV-2 at the site of infection is expected to contribute
significantly to controlling HSV-2 and HIV transmission.