Novel RNA Interference (RNAi)-Based Nanomedicines for Treating Viral Infections - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 210

dosing regimen was reduced 10 fold to 3 mg/kg three times daily and a
single weekly injection was sufficient to maintain greater than 10-fold
inhibition of HBV antigen production up to 6 weeks.
Complexing siRNAs to the liver-specific protein apolipoprotein
A-I (apo A-I) is yet another method that has been utilized to target
delivery of anti-HBV siRNAs to the liver. Apo A-I was formulated onto
nanoparticles carrying siRNAs, which were then administered i.v. to
mice expressing replicating HBV in the liver [65]. In vivo experiments
with luciferase reporter siRNAs demonstrated that siRNAs delivered
by apo A-I nanoparticles are eff ectively and specifically delivered
to the liver. Moreover, delivery of anti-HBV siRNAs with these
nanoparticles significantly reduced HBsAg for up to 8 days post-
treatment.
Another method for targeting delivery that is gaining in popularity
is the use of cell type-specific antibodies. A slight modification of
this method has been used to deliver siRNAs specifically to HBV
infected hepatocytes. Rather than delivering siRNAs to hepatocytes
in general, one group has used a humanized anti-HBV single-chain
antibody to deliver siRNAs specifically to HBsAg-positive cells in vivo
[116]. siRNA delivered with this method were efficiently delivered
to HBs-Ag-positive cells and inhibited HBV gene expression in HBV
transgenic mice. All of the aforementioned studies suggest that
siRNAs are a feasible antiviral therapy for the treatment of HBV
and that several methods can be utilized to target delivery of these
siRNAs, therefore increasing potency while reducing toxicity.

7.2.2 Human Papillomavirus (HPV)

HPV is one of the most prevalent sexually transmitted diseases
in the world [14]. HPV causes cervical cancer; the second leading
cause of cancer related deaths in women [122]. A HPV vaccine for
immunization of women between 9 and 26 years of age exists;
however, there are currently no eff ective therapies for individuals
already infected with HPV and a small fraction of those patients will
develop cancer in a decade or two. More than 200 genotypes of HPV
exist, but HPV-16 and HPV-18 alone account for approximately 70%
of cervical cancers worldwide [122]. HPV is a member of the family
Papovaviridae , a group of double-stranded circular DNA viruses. The
DNA genome of HPV encodes 6 early genes (E1, E2, E4, E5, E6 and
E7) and two late genes (L1 and L2) [14]. The oncogenic properties of