eir chemical make-up and biological properties can be found elsewhere^[@CR42],[@CR43],[@CR44],[@CR45]^. Among the most common are lipid-based carriers or cholesterol conjugates to the sense strand of the duplex. Cholesterol-conjugated siRNAs, which are commercially available, enable improved uptake to the liver as they are bound by low-density lipoprotein (LDL) in serum and LDL uptake in the liver is robust^[@CR46]^. Lipophilic siRNAs can also bind high-density lipoprotein (HDL); this can target siRNAs to tissues with HDL receptors, such as gut^[@CR47]^, kidney^[@CR47]^ and vaginal^[@CR48]^ epithelial cells and oligodendrocytes in the brain^[@CR49]^.

Exciting data in nonhuman primates showed that a single delivery of siRNAs complexed into [stable nucleic acid lipid particles](#Glos9){ref-type="list"} (SNALPs) reduced target gene expression for almost 2 weeks^[@CR50]^. Recently the same delivery strategy was used successfully to protect nonhuman primates from a lethal challenge of Ebola virus, using siRNAs targeting the expression of three Ebola virus proteins^[@CR51]^. Improvements in SNALPs that reduce the doses required for effective silencing in nonhuman primates by \~tenfold will augment the clinical utility of these reagents^[@CR40]^.

Complexing siRNAs with carriers also provides opportunities for targeting specific cells or, in the case of cancer, tumour beds. In the first in-human study, nanoparticles designed for enhanced uptake to cancer cells by using transferrin-receptor-targeting ligands showed reduced levels of the target mRNA and evidence for siRNA-mediated cleavage of that target^[@CR52]^. As the study continues, it will be interesting to learn the pharmacokinetics of the siRNAs in additional patients and to see the clinical effects of the therapy. Other carriers for tissue-specific targeting include aptamers^[@CR53],[@CR54]^, antibodies^[@CR55],[@CR56],[@CR57],[@CR58]^, peptides and proteins^[@CR52],[@CR59]^, and oligonucleotide agonists^[@CR36]^. Some are synthetically linked to the siRNAs, as 