Aptamer-Mediated siRNA Targeting - RNA Interference from Biology to Therapeutics - page 212

nanocomplex with a peak hydrodynamic diameter of ~140 nm was formulated by
incorporating both ALK (anaplastic lymphoma kinase) siRNA and a CD30 RNA
aptamer into nano-sized polyethylenimine-citrate carriers via noncovalent interac-
tion [ 94 ]. The selective uptake of the nanocomplex and specific ALK gene silencing
effects were observed in ALCL cells (anaplastic large cell lymphoma) expressing
the CD30 receptor [ 95, 96 ] .

10.4 Concluding Remarks and Future Perspectives

According to a PubMed search with “aptamer” as keyword, more than 2,700 publi-
cations indicate that the field of aptamer research has generated lots of interest in the
scientific community. Aptamers have a number of advantages in their clinical usage
over their antibody counterparts, and due to the relatively simple chemistry, aptamer-
based applications will become more tunable and accessible compared to antibod-
ies. However, several important issues limit the applications of aptamers. These
include a reduced bioavailability compared to antibodies as well as high cost for the
scale-up chemical syntheses of these RNA compounds. In this regard, increasing
efforts are being made toward the development of efficacious selection methodolo-
gies to identify new aptamers with high affinity and novel chemical synthesis meth-
ods. For example, live cell-SELEX has offered very promising results in recent
years and automated SELEX workstations are used to rapidly select aptamers for
multiple targets. As these technologies are improved, we expect that the develop-
ment and commercialization of aptamers will accelerate their clinical applications.
Interest in the therapeutic potential of nucleic acid-based agents, such as siRNAs,
microRNAs, aptamers, antisense DNAs, mRNAs, and ribozymes has grown over the
past two decades. With the technological maturation and increasing knowledge of
RNAi as well as aptamers and their mechanism of action, it seems natural to partner
multiple therapeutic nucleic acids (e.g., aptamers and siRNAs) to expand the poten-
tial for therapeutic efficacy. Because the building blocks for both are RNA mole-
cules, combining cell-specific aptamers with RNAi-based therapeutic agents is facile
and provides flexibility for achieving targeted delivery of siRNAs in the desired cells
or tissue. Currently, siRNAs have been attached to cell-specific aptamers either
through direct conjugation to the aptamer, or via functionalized groups appended on
the aptamer. Additionally, nucleic acids also can be fused to polyethylene glycol
(PEG) or assembled into a nanocarrier, thus reducing kidney clearance and increas-
ing their propensity to circulate and distribute into tumor tissues. For example, a
precisely engineered nanocarrier system functionalized with a cell-specific aptamer
not only has an appropriate nanoscale size, thereby allowing preferential accumula-
tion in the tumor in the passive target mode, but also can selectively recognize and
bind to surface proteins on the targeted cells via the interaction of the ligand and cell-
surface receptor, thus facilitating selective internalization. Therefore, the combined
advantages of aptamers as targeting agents and the utility of nanoparticles as drug
carriers make combining these into drug delivery vehicles very attractive.