RNAi as New Class of Nanomedicines - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 173

bound to the RVG-polyarginine fusion molecule protected mice from
a subsequent lethal challenge with infectious JEV. Recently, the RVG-
polyarginine fusion molecule was used to deliver siRNAs targeting
tumor necrosis factor α (TNFα) to macrophage/microglial cells
expressing the nicotine acetylcholine receptor [85]. The systemic
administration of the TNFα siRNA complexed with the RVG-9dR
fusion molecule inhibited neuroinflammation in lipopolysaccharide
(LPS)-treated mice. In a similar manner, a 12-amino acid peptide
(DC3) identified from a phage display peptide library that specifically
binds to a cell surface antigen on dendritic cells was fused to the
nona-D-arginine peptide (DC3-9dR) [139]. This fusion molecule
was used to deliver siRNAs targeting the Dengue virus envelope
to monocyte-derived dendritic cells, CD34+ hematopoietic stem
cell-derived Langerhan DCs, and peripheral blood DCs resulting
in the efficient inhibition of Dengue virus replication. The delivery
of siRNAs targeting TNFα to DCs inhibited Dengue virus-induced
TNFα in cultured cells and poly(I:C)-induced TNFα expression in
humanized mice.

6.2.3 Aptamer-Mediated siRNA Delivery

Aptamers are structured nucleic acid molecules (RNA or DNA
aptamers) in vitro selected through multiple rounds to bind with
high affinity to specific target molecules in a process termed the
systematic evolution of ligands by exponential enrichment or SELEX.
RNA aptamers can be produced by in vitro transcription and readily
purified in high yield. This ease of production gives aptamers an
advantage over ligands and antibodies, which need to be purified
from cultured mammalian cells, insect cells, yeast or bacteria
and require extensive purification before they are amenable for
therapeutic applications. An aptamer, which efficiently binds to the
prostate-specific membrane antigen (PSMA), eff ectively delivered
anti-tumor siRNAs (for example, siRNAs targeting PLK1 or BCL2) to
PSMA-expressing tumor cells resulting in a regression in tumor size
in a mouse prostate cancer model [109]. Modification of the siRNA
structure and the appending of a PEG moiety helped to increase the
silencing activity and improve the bioavailability of these molecules
[25]. In a variation of these experiments, a streptavidin-biotin
bridge was employed to connect the PSMA aptamer to siRNAs [22].
Aptamers targeting the HIV-1 envelope glycoprotein (gp120) have