Editing Small interfering RNA (section)

===Innate immunity===
Introduction of too many siRNA can result in nonspecific events due to activation of innate immune responses.<ref name=pmid22432611>{{cite journal | vauthors = Whitehead KA, Dahlman JE, Langer RS, Anderson DG | title = Silencing or stimulation? siRNA delivery and the immune system | journal = Annual Review of Chemical and Biomolecular Engineering | volume = 2 | issue = 1 | pages = 77–96 | date = 17 June 2011 | pmid = 22432611 | doi = 10.1146/annurev-chembioeng-061010-114133 | s2cid = 28803811 }}</ref> Most evidence to date suggests that this is probably due to activation of the dsRNA sensor PKR, although retinoic acid-inducible gene I (RIG-I) may also be involved.<ref>{{cite journal | vauthors = Matsumiya T, Stafforini DM | title = Function and regulation of retinoic acid-inducible gene-I | journal = Critical Reviews in Immunology | volume = 30 | issue = 6 | pages = 489–513 | date = 2010 | pmid = 21175414 | pmc = 3099591 | doi = 10.1615/critrevimmunol.v30.i6.10 }}</ref> The induction of cytokines via toll-like receptor 7 (TLR7) has also been described. Chemical modification of siRNA is employed to reduce in the activation of the innate immune response for gene function and therapeutic applications.  One promising method of reducing the nonspecific effects is to convert the siRNA into a microRNA.<ref>{{cite journal | vauthors = Barøy T, Sørensen K, Lindeberg MM, Frengen E | title = shRNA expression constructs designed directly from siRNA oligonucleotide sequences | journal = Molecular Biotechnology | volume = 45 | issue = 2 | pages = 116–20 | date = June 2010 | pmid = 20119685 | doi = 10.1007/s12033-010-9247-8 | s2cid = 24309609 }}</ref> MicroRNAs occur naturally, and by harnessing this endogenous pathway it should be possible to achieve similar gene knockdown at comparatively low concentrations of resulting siRNAs. This should minimize nonspecific effects.