Table 4.
Target gene | RNAi inducer (length) | Promoter | Vector | Model | Delivery methods | Inhib. of virus prod. (fold) | Reference |
In vitro studies Viral gene | |||||||
Leader, TRS, 3’-UTR, S | siRNA (21 bp) | - | - | Vero E6 | Transfection | 9 | [110] |
N | shRNA (20 bp) | U6 | Plasmid | 293 | Transfection | NR | [112] |
E, M, N | siRNA (21 bp) | - | - | Vero E6 | Transfection | > 4 | [113] |
P | shRNA (19 bp) | H1 | Plasmid | Vero | Transfection | > 100 | [114] |
S | shRNA (22 bp) | U6 | Plasmid | Vero E6, 293T | Transfection | -6 | [115] |
Rep | siRNA (21 bp) | - | - | FRhk-4 | Transfection | > 12 | [118] |
Cellular gene | |||||||
CHC | siRNA (25 bp) | - | - | HepG2, COS7 | Transfection | -1 | [116] |
In vivo studies | |||||||
S, NSP12 | siRNA (21 bp) | - | - | BALB/C mouse, Rhesus macaque (Macaca mulatta) | i.t.1 and i.n.2 administration | 3 | [119] |
The fold inhibition of virus production refers to the results obtained with the most potent siRNA/shRNA. All siRNAs were prepared by chemical synthesis unless indicated otherwise. TRS: Transcription-regulating sequence; UTR: Untranslated region; S: Spike protein; N: Nucleocapsid protein; NR: Not reported; E: Envelope protein; M: Membrane protein; P: RNA polymerase; Rep: Replicase; FRhk-4: Fatal Rhesus monkey kidney cells; CHC: Clathrin heavy chain; NSP: Non-structural protein; i.t.: Intratracheal; i.n.: Intranasal.
siRNA and target-sequence containing reporter plasmid co-administered intratracheally into mouse lungs in D5W or Infasurf solution;
siRNA instilled intranasally to monkey in D5W solution with different dosing regimens.