Novel RNA Interference (RNAi)-Based Nanomedicines for Treating Viral Infections - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 222

targeting the tat/rev common exon and the HIV host dependency
factors CD4 and transportin 3. Further, because both the aptamer
and the siRNA can inhibit HIV-1 replication by respectively blocking
the gp120-CD4 receptor interaction and silencing target gene
expression, this novel anti-gp120 aptamer-siRNA chimera possessed
a dual inhibitory function. i.v. injection of these chimeras in the 4 th
week of infection into humanized mice dramatically decreased viral
loads to undetectable levels within a week after administration and
completely prevented T-cell depletion (unpublished observations)
[134].
Taken together, these studies show that gene therapy using RNAi
is a feasible approach to control HIV infection.

7.5 Negative-Sense RNA Viruses

7.5.1 Respiratory Syncytial Virus

Globally, RSV is the leading cause of acute lower respiratory infections
with an estimated 33.5 million new episodes and 199,000 deaths in
children under five in 2005 [93]. Currently there are only two FDA-
approved drugs for the treatment of RSV, a monoclonal antibody
Palivizumab for use in high-risk infants and Ribavirin for severe
infections though not recommended by the American Academy
of Pediatrics due to the limited evidence of benefit, high cost, and
potential toxic eff ects [35]. RSV is a member of the Paramyxoviridae
family with a negative sense single stranded RNA genome encoding
10 viral proteins. Of these, the G glycoprotein distinguishes the two
antigenic subgroups, RSV-A and RSV-B, within the RSV serotype. The
virus replicates in the outermost layer of the respiratory epithelium
that lines the human respiratory tract that is easily accessible to
nasally applied naked siRNA [10]. RNAi is therefore an option for
RSV treatment.
ALN-RSV01 is a siRNA directed against a highly conserved
sequence in the nucleocapsid (N) protein gene sequence [1]. In a
murine prophylaxis model, a 100 μg dose of ALN-RSV01 given i.n.
4 hours prior to infection with RSV A2 highly reduced titers in the
lung. ALN-RSV01 also proved efficacious when administered in 40
μg doses on days 1, 2, and 3 post-infection (p.i.). ALN-RSV01 became
the first siRNA-based antiviral to be tested in two human clinical