TABLE 1.
Reports using synthetic siRNAs in mammals
| Target(s) | System | Route/delivery | IFN studied | Modified siRNAs | Reference and year |
|---|---|---|---|---|---|
| Luc | Mouse—reporter | IV–hydrodynamic | No | No | [148] 2002 |
| Luc, EGFP | Mouse—reporter | IV–hydrodynamic | No | No | [149] 2002 |
| EGFP | Mouse—reporter | DIT–cationic lipid | No | No | [222] 2002 |
| Luc | Mouse—reporter | IV–hydrodynamic | No | Yes | [62] 2004 |
| Luc, Fas | Mouse—reporter | IV–hydrodynamic | Yes | No | [91] 2004 |
| Luc | Mouse, rat, primate—reporter | IV–hydrodynamic | No | No | [155] 2004 |
| EGFP, RFP | Rat—reporter | IV–hydrodynamic | No | No | [164] 2005 |
| Luc | Mouse—reporter | IV–hydrodynamic; DIT–electroporation | No | No | [163] 2005 |
| EGFP, Tnf | Mouse—reporter | IV, IP–DOTAP liposomes | Yes | No | [92] 2003 |
| Luc, EGFP, Gapdh | Mouse—reporter | IM–electroporation | No | No | [167] 2004 |
| EGFP | Mouse—reporter | IM–electroporation | No | No | [171] 2005 |
| EGFP | Mouse—reporter | Cardiac sonoporation | No | No | [173] 2005 |
| EGFP | Mouse—reporter | IP–virosomes | No | No | [145] 2006 |
| Abcb1a (Mdr1a/1b) | Mouse—liver | IV–hydrodynamic | No | No | [162] 2005 |
| Rho | Mouse—liver plasmid codelivery | IV–hydrodynamic | No | No | [161] 2005 |
| Gapdh | Mouse—lung | IN–InfaSurf | No | No | [215] 2004 |
| Tgfb1, EGFP, Luc | Rat—glomerulonephritis | Renal artery electroporation | No | No | [168] 2005 |
| Fas | Mouse—hepatitis | IV–hydrodynamic | No | No | [150] 2003 |
| Casp8 | Mouse—hepatitis | IV–hydrodynamic | No | No | [152] 2003 |
| Fas | Mouse—ischemia–reperfusion injury | IV–hydrodynamic | No | No | [156] 2004 |
| Casp8, Casp3 | Mouse—ischemia–reperfusion injury | IV–hydrodynamic | No | No | [154] 2004 |
| Hmox1 | Mouse—ischemia–reperfusion injury | IN–naked | No | No | [223] 2004 |
| Hsf1 | Mouse—ischemia–reperfusion injury | IP–cationic lipid | No | No | [115] 2005 |
| P4ha2 | Mouse—ischemia–reperfusion injury | IP–cationic lipid | No | Yes | [224] 2006 |
| Tlr4, Bcl2, Irak3 | Mouse—immune stimulation | IV–DOTAP liposomes | Yes | No | [93] 2005 |
| Mif | Mouse—transplant | TOP–cationic lipid | No | No | [225] 2005 |
| Tbx21 | Mouse—multiple sclerosis | IV–naked | Yes | No | [226] 2004 |
| Casp8, Fas, EGFP | Mouse—CLP sepsis and reporter | IV–hydrodynamic | No | No | [160] 2005 |
| Casp8, Fas | Mouse—CLP sepsis | IN–naked intratracheal | Yes | No | [227] 2005 |
| Cxcl1 (KC), Cxcl2 (MIP2) | Mouse—CLP sepsis | IN–naked intratracheal | Yes | No | [228] 2005 |
| Il12b (IL-12p40) | Mouse—LPS/sepsis | IP–cationic lipid | Yes | No | [114] 2004 |
| Tnf, EGFP | Mouse—LPS/sepsis | IV, IP–DOTAP liposomes | Yes | No | [198] 2003 |
| Tnf, Luc, EGFP | Mouse—arthritis | IA–electroporation | No | No | [170] 2005 |
| Tnf | Rat—arthritis | IA–electroporation + cationic lipid | No | No | [172] 2005 |
| Apob | Mouse—metabolic | IV–Chol conjugated | No | Yes | [65] 2004 |
| Apob | Mouse—metabolic | IV–SNALP | Yes | Yes | [96] 2006 |
| Avpr2 | Mouse—metabolic | IV–DOTAP liposomes | No | No | [229] 2005 |
| Cav1 | Mouse—metabolic | IV–DDAB liposomes | No | No | [230] 2006 |
| Cyba | Rat—metabolic | IV–HD, cationic lipid | Yes | No | [165] 2006 |
| RRM2 | Mouse—tumor | IV–naked | No | No | [188] 2004 |
| CEACAM6 | Mouse—tumor | IV–naked | No | No | [189] 2004 |
| CXCR4 | Mouse—tumor | IV–naked | No | No | [190] 2005 |
| BCL2 | Mouse—tumor | IV, SC–LIC-101 liposomes | No | No | [231] 2004 |
| BCL2 | Mouse—tumor | IP–naked | No | No | [232] 2005 |
| RAF1 | Mouse—tumor | IV–CCLA liposomes | No | No | [128] 2005 |
| RAF1 | Mouse—tumor | IV–CCLA liposomes | No | No | [127] 2005 |
| RAF1 | Mouse—tumor | DIT–peptide carrier | No | No | [211] 2005 |
| EPHA2 | Mouse—tumor | IV–DOPC liposomes | No | No | [192] 2005 |
| EWS-FLI1 | Mouse—tumor | IV–cyclodextrin polyplex | Yes | No | [134] 2005 |
| Vegfa, Mdm2, Myc, EGFP, gag | Mouse—tumor | IV–Fab-protamine | Yes | No | [138] 2005 |
| EZH2, PIK3CA, Luc | Mouse—tumor | IV–atelocollagen | Yes | No | [143] 2005 |
| CTNNB1 (β-catenin) | Mouse—tumor | IP–cationic lipid | No | No | [113] 2003 |
| ERBB2 (HER-2) | Mouse—tumor | IP–PEI | No | No | [199] 2005 |
| Csf1, Csf1r | Mouse—tumor | DIT–naked | No | No | [210] 2004 |
| RAD51 | Mouse—tumor | DIT–HVJ viral envelope | No | No | [146] 2005 |
| FGF4 | Mouse—tumor | DIT–atelocollagen | No | No | [233] 2004 |
| VEGF | Mouse—tumor | DIT–atelocollagen | No | No | [212] 2004 |
| VEGFR2 (Kdr) | Mouse—tumor | IV–RPP-polyplex | No | No | [130] 2004 |
| Vegfa, Luc | Mouse—tumor | IV, IP, SC, DIT–naked | No | No | [187] 2003 |
| Vegfa, Sst | Mouse—tumor | DIT–jetSI | No | No | [234] 2005 |
| Edg1 (S1P1) | Mouse—tumor | DIT–DOTAP liposomes | No | No | [235] 2004 |
| Rhoa, Rhoc | Mouse—tumor | DIT–cationic lipid | No | No | [236] 2005 |
| Plk1 | Mouse—tumor | TOP–cationic liposomes, bladder | No | No | [237] 2005 |
| VEGF, EGFP | Mouse—ocular neovascularization | IO–cationic lipid | No | No | [200] 2003 |
| Vegfa, Flt1 (VEGFR1), Kdr (VEGFR2) | Mouse—ocular neovascularization | IO–naked; IV–polyplex | No | No | [202] 2004 |
| VEGFR1 | Mouse—ocular neovascularization | IO–naked | No | Yes | [201] 2006 |
| TGFBR2 | Mouse—ocular fibrosis | IO–cationic lipid | No | No | [238] 2004 |
| Bax, Apaf1, Jun | Rat—ocular axotomy apoptosis | IO–naked | No | No | [239] 2005 |
| App | Rat—amyloid, CNS | IO–cationic lipid | No | No | [240] 2006 |
| Bax, Bak | Mouse—apoptosis and immunization | Dermal–gene gun | No | No | [174] 2005 |
| GJB2 | Mouse—auditory | TOP–DOTAP liposomes | No | No | [118] 2005 |
| Agrp | Mouse—CNS metabolic | CNS–naked | No | No | [241] 2002 |
| Slc6a3 | Mouse—CNS behavioral | CNS–naked | No | Yes | [206] 2004 |
| Slc6a4 | Mouse—CNS behavioral | CNS–naked | No | Yes | [207] 2005 |
| Luc | Mouse—CNS reporter | CNS–PEI, DOPE | No | No | [116] 2005 |
| Drd1a | Rat—CNS behavioral | CNS–naked | No | No | [208] 2003 |
| P2rx3 | Rat—CNS behavioral | CNS–naked | No | Yes | [205] 2004 |
| Adra2a | Rat—CNS behavioral | CNS–naked | No | No | [242] 2004 |
| Oprd1 | Rat—CNS behavioral | CNS–cationic lipid | No | No | [117] 2005 |
| Mc4r | Rat—CNS behavioral | CNS naked, cationic lipid, DOTAP liposome | No | No | [209] 2005 |
| Gria2, Ptgs1 | Rat—CNS physiology | CNS electroporation | No | No | [169] 2005 |
| Hepatitis B | Mouse—virus | IV–hydrodynamic | No | No | [151] 2003 |
| Hepatitis B | Mouse—virus | IV–hydrodynamic | No | No | [153] 2003 |
| Hepatitis B, meri-1 | Mouse—virus | IV–hydrodynamic | No | No | [112] 2005 |
| Hepatitis B | Mouse—virus | IV–hydrodynamic | No | Yes | [63] 2005 |
| Hepatitis B | Mouse—virus | IV–SNALP | Yes | Yes | [52] 2005 |
| Influenza | Mouse—virus | IV–PEI | Yes | No | [197] 2004 |
| Influenza | Mouse—virus | IV–deacyl-PEI | No | No | [131] 2005 |
| Influenza | Mouse—virus | IV–hydrodynamic; IN–cationic lipid | No | No | [157] 2004 |
| CVB3 | Mouse—virus | IV–hydrodynamic | No | No | [159] 2005 |
| West Nile virus | Mouse—virus | IV–hydrodynamic | No | No | [158] 2005 |
| HSV2 | Mouse—virus | TOP–cationic lipid | Yes | No | [119] 2006 |
| RSV, PIV | Mouse—virus | IN–naked | No | No | [216] 2005 |
| SARS | Primate—virus | IN–naked | No | No | [217] 2005 |
| Berghepain 1 and 2 | Mouse—malaria | IV–naked | No | No | [186] 2003 |
IFN, interferon or other cytokine assay performed to assess innate immune activation; Naked, low-pressure administration without delivery assistance; CNS, direct injection into the central nervous system (intrathecal, intraventricular, or stereotactic); DIT, direct intratumor injection; IA, intraarticular injection (joint); IM, intramuscular injection; IN, intranasal/respiratory infusion; IO, intraocular administration (subretinal, subconjunctival, intravitreous injections, etc.); IP, intraperitoneal injection; IV, intravenous injection; SC, subcutaneous injection; TOP, topical application to epithelial surface.