Table 3.
Pre-clinical therapeutic CRISPRa and CRISPRi studies
| Reference | CRISPRa/i construct | Cells/model | Purpose |
|---|---|---|---|
| Heman-Ackah et al.35 | dSpCas9-VPR, dSpCas9-KRAB | human iPSC-derived neurons | CRISPRa/i for precise modulations of endogenous gene expression in fate-committed iPSC-derived neurons |
| Liu et al.62 | dSpCas9-10xGCN4 (SunTag) + scFv-GCN4-sfGFP-VP64 | mouse embryonic fibroblasts (MEFs), tail tip fibroblasts (TTFs) | reprogramming of fibroblasts toward pluripotency |
| Yoshida et al.123 | dSpCas9-KRAB | lung SCC cells, pulmonary adenocarcinoma cells, esophageal SCC cells, foreskin fibroblasts |
CRISPRi targeting of ΔNp63 for treatment of squamous cell carcinoma |
| Moreno et al.36 | KRAB-dSpCas9 | C57BL/6J mice | targeted repression of Nrl to mediate in situ reprogramming of rod cells into cone-like cells |
| Matharu et al.44 | dSpCas9-VP64, dSaCas9-VP64 | neuro-2a, Sim+/− mice | promoter or enhancer activation to rescue haploinsufficiency |
| Chung et al.34 | dSpCas9-KRAB | white adipocytes | inhibition of Fabp4 to ameliorate obesity, inflammation, hepatic steatosis, and insulin resistance |
| Wang et al.71 | dSpCas9-VP64, MCP-p65-HSF1 (SAM) | C57BL/6J mice | multiplexed activation of endogenous genes to elicit potent antitumor immunity |
| Hsu et al.67 | dSpCas9-VP64, MCP-p65-HSF1 (SAM) | rat bone marrow-derived stem cells | enhancement of BMSC osteogenesis and promotion of calvarial bone regeneration |
| Di Maria et al.58 | dSaCas9-VPR, dSpCas9-VPR | C57BL/6 mice | overexpression of CB1 receptors in neurons |
| Colasante et al.48 | dSpCas9-VP160 | in vivo mouse study | in vivo CRISPRa to decrease seizures and rescues cognitive deficits in a rodent model of epilepsy |
| Nguyen et al.54 | dSpCas9-VPR, dSaCas9-VPR, dSt1Cas9-VPR, dNmCas9-VPR | adipose-derived stem cells | activation of long non-coding RNA DANCR to promote bone regeneration |
| Zhou et al.47 | dSpCas9-VP64 | mice astrocytes (in vivo) | in vivo reprogramming of astrocytes to motor neurons |
| Gemberling et al.75 | dSpCas9-p300, dSaCas9-KRAB | in vivo mouse model | creation of transgenic mouse models for CRISPRa and CRISPRi |
| Cui et al.32 | dSpCas9-VPR, dSaCas9-VPR, dSpCas9-KRAB | MCF7, MDA-MB-231, HCC202, HEK293T | dual CRISPR interference and activation for targeted reactivation of X-linked endogenous FOXP3 in human breast cancer cells |
| Sokka et al.46 | dSpCas9-VP192 | human fibroblasts | reprogramming of fibroblasts into human pluripotent stem cells |
| Urrutia-Cabrera et al.53 | dSpCas9-VPR | PBMC-iPSCs | improved induced pluripotent stem cell differentiation into neurons |
| Drobna-Śledzińska et al.33 | dSpCas9-KRAB | Jurkat, ALL-SIL | inhibition of miRNAs and miRNA clusters |
| Thege et al.68 | dSpCas9-VP64, MCP-p65-HSF1 (SAM) | in vivo mouse model | activation enables rapid evaluation and functional validation of putative oncogenes in vivo |
| Giehrl-Schwab et al.72 | dSpCas9-VPR, MCP-p65-HSF1 (SAM) | mouse primary cortical astrocytes | rescue of Parkinson’s disease motor symptoms by astrocyte reprogramming |
| Deng et al.70 | dSpCas9-VP64, MCP-p65-HSF1 (SAM) | dSpCas9-VP64 (SAM) transgenic mice | mouse model for aggressive lymphoma and interrogation of venetoclax resistance |
| Schoger et al.57 | dSpCas9-VPR | transgene mouse model | enhancing cardiomyocyte transcription in vivo |
| Ding et al.43 | dSpCas9-VP64, dSpCas9-KRAB-MeCP2 | KAI3, NUNK1, SNT16 cells | insight into the regulation of Epstein-Barr virus latency gene expression |
| Jaudon et al.51 | dSpCas9-VP64 | Itgb3 KO mice/HET mice | activation of autism gene Itgb3 restores cortical network excitability via mGluR5 signaling |
| Susco et al.56 | dSpCas9-VPR | hPSCs | uncovering specific areas of molecular convergence between Down syndrome and Fragile X syndrome |
| Zhou et al.65 | dSpCas9-10xGCN4 (SunTag) + scFv-GCN4-sfGFP-p65-HSF1 | mouse astrocytes and neurons in vivo | activation of multiple genes and long noncoding RNAs in mice to convert astrocytes into neurons for studying complex gene networks in the brain |
| Wangensteen et al.124 | dSpCas9-10xGCN4 (SunTag) + scFv-GCN4-sfGFP-VP64 | mouse hepatocytes in vivo | activation of genes that influence liver repopulation and carcinogenesis |