text: RNA interference(RNAi) is a process that occurs naturally within the cytoplasm inhibiting gene expression at specific sequences.  Regulation of gene expression through RNAi is possible by introducing small interfering RNAs(siRNAs), which effectively silence expression of a targeted gene.  RNAi activates the RNA-induced silencing complex(RISC) containing siRNA, siRNA derived from cleaved dsRNA.  The siRNA guides the RISC complex to a specific sequence on the mRNA that is cleaved by RISC and, consequently, silences those genes.
  However, without modifications to the RNA backbone or inclusion of inverted bases at either end, siRNA instability in the plasma makes it extremely difficult to apply this technique in vivo.  Pattern recognition receptors(PRRs), which can be grouped as endocytic PRRs or signaling PRRs, are expressed in all cells of the innate immune system.  Signaling PRRs, in particular, include Toll-like receptors(TLRs) and are involved primarily with identifying pathogen-associated molecular patterns(PAMPs).  For example, TLRs can recognize specific regions conserved in various pathogens, recognition stimulating an immune response with potentially devastating effects to the organism.  In particular, TLR 3 recognizes both dsRNA characteristic of viral replication and siRNA, which is also double-stranded. In addition to this instability, another limitation of siRNA therapy concerns the inability to target a tissue with any specificity.
  SNALPs, though, may provide the stability and specificity required for this mode of RNAi therapy to be effective.  Consisting of a lipid bilayer, SNALPs are able to provide stability to siRNAs by protecting them from nucleases within the plasma that would degrade them.  In addition, delivery of siRNAs is subject to endosomal trafficking, potentially exposing them to TLR3 and TLR7, and can lead to activation of interferons and proinflammatory cytokines.  However, SNALPs allow siRNA uptake into the endosome without activating Toll-like receptors and consequently stimulating an impeding immune response, thus enabling siRNA escape from the endosome.