Table 2.

Preclinical studies of miRNA-based therapeutics

Therapy	Delivery method	Targets	Efficacy of delivery	In vitro results	In vivo results	References
miR-22 mimic	G7 poly(amidoamine) dendrimer nanoparticles	CRTC1, FLT3, MYCBP	N/A	N/A	↑ Survival in MV4-11 xenotransplantation mouse models; ↑ Survival (40% cure rate) in primary mouse AML (MLL-AF9 and AE9a) transplant models	22
miR-29b mimic	Transferrin-conjugated anionic lipid-based nanoparticle	DNMT3A, DNMT3B, DNMT1, SP1, CDK6, FLT3, KIT	>100-fold ↑ in vitro	↓ Cell proliferation and ↓ colony formation in Kasumi-1, OCI-AML3, and MV4-11 cells	↑ Survival and ↓ splenomegaly in NSG mice xenografted with MV4-11 cells	69
			20-fold ↑ in vivo	↓ Cell viability in primary AML samples; pretreatment ↑ efficacy of decitabine treatment	Pretreatment ↑ efficacy of decitabine treatment
miR-21/miR-196b antagomiRs	Naked antagomiR delivered via implanted osmotic pumps	N/A	60%-80% ↓ of miRNAs in peripheral WBCs in vivo	↓ Colony formation in HOXA9, Nup98-HOXA9, or MLL-AF9–transduced mouse Lin– BM cells	Cured MLL-AF9 transplanted primary mouse AML; ↑ survival in combination with induction chemotherapy in MLL-AF9 xenotransplantation model	71
miR-126 antagomiR	Transferrin or CD45.2- conjugated anionic lipid-based nanoparticle	MMP7, CHD7, JAG1	80% ↓ in primary AML blasts in vitro; 50% ↓ in BM and spleen in vivo	↓ Long-term colony formation, ↓ self-renewal capacity, and ↓ quiescence of LSCs	↑ Survival in NSG mice engrafted with human AML primary blasts and MLL FLT3-ITD mouse model	33
miR-181a mimic	Transferrin-conjugated anionic lipid-based nanoparticle	KRAS, NRAS, MAPK1	2.6-fold ↑ in BM and 35-fold ↑ in spleen in vivo	↓ Cell proliferation and ↓ colony forming in KG1a, MV4-11, OCI-AML3 cell lines; ↑ apoptosis in primary AML blasts	↑ Survival and ↓ splenomegaly in NSG mice xenografted with MV4-11 cells	70

This table summarizes the results from selected pre-clinical miRNA-based therapies, including information such as method of delivery, miRNA targets (direct and indirect), efficacy of delivery, and in vivo/in vitro results.

BM, bone marrow; N/A, not applicable; WBC, white blood cell.