TABLE 1.
Potential targeted therapeutics for CRISPR-Cas systems
| Organism | CRISPR system | Gene target | Finding | Reference |
|---|---|---|---|---|
| E. coli, S. enterica | Type I-E (Cas3) | ftsA, asd, msbA, nusB, fucP, ogr, groL, arpA, PentC, phoH, PppsR | Selective removal of individual strains in pure and mixed cultures | Gomaa et al. (46) |
| EHEC, E. coli | Type II (Cas9) | eae, blaSHV-18, blaNDM-1, gyrA | Phagemid targeted to eae in vitro resulted in 20-fold reduction in EHEC and in vivo improved survival rates in Galleria mellonella; targeting of SHV-18 and NDM-1 was bactericidal | Citorik et al. (47) |
| E. coli | Type I-E (Cas3) | blaNDM-1, blaCTX-M-15 | Eliminated antibiotic resistance plasmids, leading to enrichment of antibiotic-sensitive bacteria using CRISPR-Cas along with temperate and lytic bacteriophages | Yosef et al. (48) |
| E. coli | Type II (Cas9) | blaTEM, blaSHV | Restored β-lactam sensitivity in ESBL-producing E. coli | Kim et al. (49) |
| S. aureus | Type II (Cas9) | aph-3, mecA | Phagemid delivery to selectively kill virulent and avirulent Staphylococcus aureus and to eliminate mecA gene without killing host | Bikard et al. (50) |
| HIV-1 | Type II (Cas9) | LTR U3 region | Inactivated gene expression and replication in infected T cells and microglial cells and use of multiplex gRNAs to prevent HIV-1 infection in TZM-bI-cells | Hu et al. (51) |
| HIV-1 | Type II (Cas9) | LTR, gag, pol | Excision of chronic HIV-1 in spleen, lungs, heart, colon, and brain from humanized mice with AAV vector | Yin et al. (53) |
| HIV-1 | Type II (Cas9) | LTR | Removal of HIV-1 DNA from human peripheral blood mononuclear cells engrafted in humanized mice with multiplex of gRNAs delivered with lentivirus vector | Bella et al. (54) |
| HSV-1 | Type II (Cas9) | Essential: UL15, UL27, UL29, UL30, UL36, UL37, UL42, UL5, UL52, UL8, UL54, UL9; nonessential: US3, US8 | Simultaneous targeting of essential genes with 2 gRNAs was superior to that with 1 gRNA in clearing HSV-1-infected cells | van Diemen et al. (55) |
| HSV-1 | Type II (Cas9) | ICP0, ICP4, ICP27 | Limited HSV-1 infection cycle in human oligodendroglioma cells | Roehm et al. (56) |
| EBV | Type II (Cas9) | EBNA-1, OriP | Targeting of Burkitt lymphoma cells infected with EBV with 2 gRNAs against EBNA-1 resulted in 95% loss of EBV genome | van Diemen et al. (55) |
| CMV | Type II (Cas9) | Essential: UL44, UL54, UL57, UL70, UL105, UL86, UL84; nonessential: US6, US7, US11 | Targeting of essential genes led to inhibition of CMV replication and targeting of nonessential genes did not | van Diemen et al. (55) |
| HBV | Type II (Cas9) | Repeat region of integrated genome | Removal of integrated and episomally located HBV genome from HBV cell line | Li et al. (58) |
| HBV | Type II (Cas9) | S open reading frame | Inactivation of cccDNA of HBV in hNTCP-HepG2 cells with AAV vector | Scott et al. (59) |
| JCV | Type II (Cas9) | T-antigen | Suppressed JCV replication in HJC-2 cells using lentivirus vector delivery | Wollebo et al. (60) |
| HPV | Type II (Cas9) | E6, E7 | Targeting of E6 and E7 with gRNA delivered by lentivirus vector resulted in death of HPV-transformed cells | Kennedy et al. (61) |