Novel RNA Interference (RNAi)-Based Nanomedicines for Treating Viral Infections - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 203

Figure 7.2 Delivery of RNA-inhibition (RNAi)-mediators in vivo . (a) RNAi-
mediators can be delivered for topical applications (i) into the pulmonary
tissue using intranasal aerosols; (ii) intratracheally using a catheter through
an incision made near the throat; (iii) intracranially into the ventricular
or hippocampal areas using stereotactic techniques ; (iv) intravaginally
or intrarectally using blunt rubber tipped needles or; (v) intravitreally
in the eye. Systemic delivery is achieved using non-invasive carriers
through intraperitoneal and intravenous injections or physical methods
like hydrodynamic injections. In the case of systemic routes, delivery has
been achieved both non-specifically and through targeting ligands that
provide targeting to specific cell types. Long-term eff ects are achieved
using integrating viral vectors or plasmid vectors with a selection marker
and short-term eff ects are achieved with non-integrating viral vectors,
plasmid-expression vectors and siRNAs (in the naked form for topical
application or carrier-complexed for systemic delivery). (b) RNAi mediators
have been administered intravenously (e.g., SPC3549 in treatment of HCV),
intranasally (e.g., ALN-RSV0 for treatment of RSV), and intravitreally (e.g.,
PF-04523655 for the treatment of macular degeneration) to assess efficacy
in human subjects in clinical trials. Gene therapeutic methods have also
included the ex vivo transduction of cells like human stem cells and T cells
with lentiviral vectors expressing shRNA followed by transplantation of
autologous donors.