MicroRNA-regulated viral vectors for gene therapy

Table 1 Application of microRNA-regulated vectors for gene therapy

Target cell/tissue for therapy	miR-TS for	Number miRTS	Vector	MicroRNA-regulated transgene	De-targeted cell/tissue	Ref.
Heart
Heart	miR-122	3, 5	AAV9	EGFP, lacZ, luciferase	Liver	[67,68]
Heart	miR-122	3	AAV9	Human S100A1	Liver, skeletal muscle	[61]
	miR-206	3
Cancer
PyMT mouse breast cancer	miR-1	4	AAV9- ESGLSQS	Herpes simplex virus thymidinkinase (and ganciclovir), luciferase	Heart	[129]
Metastatic hepatocellular carcinoma model	miR-122	4	AAV8	Herpes simplex virus thymidinkinase (and ganciclovir), luciferase	Hepatocytes/liver	[128]
Glioblastoma cells in vitro	miR-128	2	Lentiviral	Herpes simplex virus thymidinkinase (and ganciclovir)	Neuronal differentiated cells	[127]
Subcutaneous fibrosarcoma xenografts	miR-122	4	Adenoviral	Luciferase	Hepatocytes/liver	[181]
Intradermal melanoma tumor	miR-122	4	Adenoviral	Herpes simplex virus thymidinkinase	Hepatocytes/liver	[87]
Human glioma xenografts	miR-31 miR-127 miR-143	3 3 3	Baculoviral	Herpes simplex virus thymidinkinase (and ganciclovir)	Astrocytes/brain	[85]
Hepatocellular carcinoma model	miR-181	2	Adenoviral	Human telomerase reverse transcriptase RNA-targeting ribozyme	Hematopoietic stem cell- and progenitor-derived blood cells	[130]
	miR-122	3			Hepatocytes/liver	[131]
HSC and iPSC
Tumor-infiltrating monocytes/macrophages	miR-126 miR-130a	2 2	Lentiviral	Interferon-α	Hematopoietic stem and progenitor cells	[134]
Differentiated myeloid cells	miR-126	2	Lentiviral	Gp91phox	Hematopoietic stem and progenitor cells	[135]
Differentiated hematopoietic cells	miR-126 miR-130a	4 4	Lentiviral	Galactocerebrosidase	Hematopoietic stem and progenitor cells	[133]
Lymphoid progenitors, myeloid cells	miR150	4	Lentiviral	GFP	Differentiated T and B lymphocytes	[132]
Post-thymic T cells	miR181a	4	Lentiviral	GFP, inhibition of negative thymic selection	Developing T cells	[182]
Myeloid cells Immature dendritic cells	miR223 miR155	4 4	Lentiviral	EGFP, NGFR	Granulocytes and monocytes, mature dendritic cells	[17]
Human fetal fibroblasts	miR-302a, d miR-142-3p	4 4	Lentiviral	EGFP, mCherry	Human ES, neural progenitors	[137]
	miR-155	4
	miR-223	4
ES, iPSC	miR-292-3p	4	Lentiviral	GFP, differentiation of ES to neural progenitors	Pluripotent cells	[138]
ES, iPSC	let-7a	4	Lentiviral	GFP	Non pluripotent cells	[136]
CNS and eye
CNS	miR-1	3	AAV9	lacZ, EGFP	Heart, liver	[69]
	miR-122	3
CNS/astrocytes	miR-124	4	Lentiviral	lacZ, glial glutamate transporter	Neurons	[141]
CNS/cortical excitatory neurons	miR-128 miR-221	4, 8, 12 4, 8	Lentiviral	EGFP	Cortical inhibitory neurons	[83]
Retina/eye	miR-124 miR-204	4 4	AAV5 AAV8	EGFP	Photoreceptors/retinal pigment epithelium	[143]
Photoreceptor/eye	miR-181c	4	AAV2 (quadY-F+T-V)	GFP	Ganglion cells and inner retina	[144]
Immune system and other applications
Skeletal muscle	miR-142-3p	2, 4, 8	AAV1	Ovalbumin human sarcoglycan	Antigen presenting cells	[152,153]
Hepatocytes/liver	miR-142-3p	4	Lentiviral	Factor IX, VIII, induction immunologic tolerance	Antigen presenting cells	[9,145,147,183]
Dendritic cells/spleen	miR-142-3p miR-122	4 4	Adenoviral	Luciferase, lacZ, combination with Cre-loxP system	Hepatocytes/liver	[86]
Neural stem cells	miR124a	4	Lentiviral	GFP, identification of neurons	Neurons	[184]
Adipose tissue	miR-122	3, 8	AAV8	Human leptin	Hepatocytes/liver	[185]
Intramuscular delivery	miR-122 miR-206	6 6	AAV8	201Ig immunoadhesin, luciferase	Liver, skeletal muscle	[186]
Human fibroblasts HFL1	miR-124	4	Lentiviral, replication deficient	Neural conversion genes Ascl1, Brn2 and Myt1L	Human induced neurons	[179]
Skeletal muscle	miR-208a	2	AAV9	Human calpain3	Heart	[81]

miR-TS: Artificial microRNA target sites; HSC: Hematopoietic stem cell; CNS: Central nervous system; AAV: Adeno-associated virus; GFP: Green fluorescent protein; EGFP: Enhanced green fluorescent protein; iPSC: Induced pluripotent stem cells; NGFR: Nerve growth factor receptor; ES: Embryonic stem cells; HFL1: Human fetal lung fibroblast 1.