Table 1.
Studies involving the in vivo delivery of CRISPR systems in breast cancer or triple negative breast cancer (TNBC) models.
Delivery Method | Subtype | Material | Applicability/ Delivery of |
Target Gene/s | In Vivo Model of Breast Cancer/TNBC | Route and Frequency of Administration |
Ref. |
---|---|---|---|---|---|---|---|
Non-viral delivery | Lipid-polymer hybrid nanoparticles | Phenylboronic acid—functionalised low molecular weight polyethyleneimine PEI 1.8k (PEI-PBA) |
dCas9-based CRISPR interference system (CRISPRi) |
miR-10b | 4T1 TNBC allograft | Intravenously Every 5 days for 28 days |
[48] |
Non-viral delivery | Nanovesicles | Tumour-derived extracellular vesicles—fusogenic anthracycline doxorubicin liposomes (T-DOX) | CRISPR/Cas9 | PD-L1 | Orthotopic 4T1 TNBC allograft | Subcutaneously 1-day interval |
[49] |
Non-viral delivery | Nanobubbles | Polyethyleneimine (PEI) | CRISPR/Cas9 | Cdh2 | Orthotopic 4T1 TNBC allograft | N/A | [50] |
Non-viral delivery | Polyethyleneimine–Bovine serum albumin-based nanoparticles |
Polyethyleneimine– Bovine serum albumin (PEI-BSA) |
CRISPR/Cas9 system in plasmid and ribonucleoprotein format |
CD81 | BALB/c mice | Intravenously One injection |
[51] |
Non-viral delivery | DNA-based nanoparticles |
Polyglycerol Dimethacrylate |
Co-delivery of Cas9/sgRNA ribonucleoprotein and DNAzyme |
PLK1
EGR-1 |
Breast cancer MCF7 xenografts | Intravenously Days 0 and 6 |
[52] |
Non-viral delivery | Targeted core-shell nanoparticles | Polyacrylaminoester (PAA) | Dual plasmids pHR-pCas9 | CTCF | Female BALB/c nude mice | Intravenously | [53] |
Non-viral delivery | Nanoparticles | Polylysine functionalised black phosphorus (PLL-PBP) |
PBP/Cas13a/ crMcl-1 complex |
Mcl-1 | TNBC MDA-MB-231 xenograft | Intratumourally Every two days for a total of 10 injections |
[54] |
Non-viral delivery | Autocatalytic brain tumour-targeted nanoparticles |
HDL-DES-MDEA polymer |
LRRC31 cDNA loaded NPs | LRRC31 | Female BALB/c nude mice | Intravenously Days 6 and 11 |
[30] |
Non-viral delivery | Polymeric nanoparticles |
Poly-β-amino ester (PBAE) | aPBAE/cas9-Cdk5 complex | Cdk5 | TNBC orthotopic 4T1 allograft | Intratumourally Days 7, 10, 13, and 16 post-inoculation of 4T1 cells |
[55] |
Non-viral delivery | Organic polymer | Poly-glycidyl methacrylate (PGMA) |
CRISPR/dCas9 conjugated to the effector domains VPR or SAM |
MASPIN
CCN6 |
Breast cancer MCF7 xenograft | Intravenously Every 5 days | [56] |
Non-viral delivery | Targeted nanolipogel (tNLGs) | Noncationic lipid bilayer and a biodegradable hydrogel core |
Three CRISPR plasmids targeted to different DNA sequences of Lnc2 | Lnc2 | Orthotopic TNBC MDA-MB-231 xenograft |
Intravenously Weekly, administered for 4 weeks |
[57] |
Viral delivery | Lentiviruses | Lentiviral pSECC vector encoding Cre and CRISPR components | sgRNA encoding vector | PTEN | Cas9-knock-in and mammary tissue-specific Cdh1F/F
female mice |
Intraductal injection |
[19] |
Viral delivery | Lentiviruses | Lentiviral | sgRNA encoding vector |
PI3KCA
Akt1 |
Mammary tissue specific of the base editor BE3 and Cre, Cas9 knock-in Brca1F/F;Trp53F/F
female mice |
Intraductal injection |
[20] |
Abbreviations: CRISPRi, clustered regularly interspaced short palindromic repeats interference; miRNA, microRNA; PD-L1, programmed death-ligand 1; SAM, synergistic activator mediator; sgRNA, single guide RNA; TNBC, triple negative breast cancer; Ref, reference; VPR, VP64-p65-Rta.