DNAzymes, Novel Therapeutic Agents in Cancer Therapy: A Review of Concepts to Applications

Table 4

In vivo applications of DNAzymes in cancer treatment.

mRNA target	DNAzyme	Animal	Xenograft	Dose regime	Outcome	Reference
β1 integrin	β1DE	BALB/cA nude (nu-/-)-B6.Cg-Foxn1^nu mice	PC-3 and CX1.1	Intratumoral administration of 1.25 μg of β1DE every second day after the tumor volume reached 150 mm^3 for three weeks	Inhibition of solid tumor growth	[26]
β1 integrin	DEβ1	BALB/cA nude (nu-/-)-B6.Cg-Foxn1^nu mice	PC-3 and HT29	Intratumoral administration of 1.25 μg of DEβ1 per tumor eight times every second day after the tumor volume reached 80-150 mm^3	Inhibition of solid tumor growth	[30]
MMP-9	AM9D	MMTV-PyMT transgenic mice	Breast tumor	When tumors were at early palpable size, intratumoral administration of 10 or 25 μg of AM9D once per week for four weeks	39.5% and 50% reduction in tumor size, respectively, 77% reduction in MMP-9 mRNA level	[38]
Egr-1	ED5	Athymic Balb/c nude mice	MCF-7	Intratumoral administration of 20 μL of ED5 with 1 μL of FuGENE6 twice a week	Inhibition of solid tumor growth	[46]
	DzF	Balb/c nude mice	MDA-MB-231	When the tumors were palpable, intratumoral administration of 10 μg of DzF twice per week in an injectate volume of 10 μL	Inhibition of solid tumor growth	[50]
VEGFR-1	DT18	Athymic nude mice	CNE1-LMP1	When the tumor volume reached 60-100 mm^3, intratumoral administration of 100 μg of DT18 with 3 μL of Fugene6, twice a week	Suppression of tumor growth, changes in tumor vasculature and vessel permeability	[53]
VEGFR-2	VEGFR2 DNAzyme	Athymic nude mice	MDA-MB-435	When the tumor was visible, four intratumoral administrations consisting his-lys polymer with 2.9 μg of DNAzyme	75% reduction in tumor growth, reduction in blood vessel density, cell death in tumor periphery	[59]
c-jun	Dz13	C57BL/J6 mice	B16F10	Commencement of the experiment, subcutaneous administration of 200 μL of vehicle containing 750 μg of Dz13 and 2.5 μL of FuGENE6 twice per week	60% reduction in tumor growth, inhibition of tumor vascular density	[58]
		Balb/c nude mice	SaOS-2	When the tumors were palpable, intratibial administration of Dz13 at 0.8 μM and caspase-2siRNA at 4 μM in 50% Matrigel	Induction of caspase-2 expression	[60]
		Mice	SW872	Commencement of the experiment, intramuscular administration of Dz13+FuGENE6 at an oligonucleotide concentration of 0.4 μM into the hind limb	Inhibition of tumor growth	[61]
		Severe-combined immunodeficient and C3H/Hen mice	T79	After 15-20 days of dermal implantation, intratumoral administration of 20 and 40 μg of Dz13 with DOTAP and DOPE twice per week	Inhibition of tumor growth and suppression of neovascularization	[66]
Bcl-xL	DT882	Balb/c athymic nude mice	PC3	When tumors reached 100-200 mm^3, a dose rate of 12.5 mg/kg/d of saline solution containing DT882 over 14 days via a ALZET osmotic pump (BioScientific)	Inhibition of tumor growth and chemosensitization	[69]
Aurora kinase A	DZ2	Balb/c nude mice	PC3	When the tumor reached about 65 mm^3, intratumoral administration of 8 μg of DZ2 daily for 14 days	Inhibition of tumor growth	[78]
Akt1	Dz2	Balb/c nude mice	CNE1-LMP1	When the tumor volume reached 60-100 mm^3, intratumoral administration of 10 μg of Dz2 with 3 μL of FuGENE6 twice per week	Inhibition of tumor growth.	[95]
PKCα	DRz4	Inbred B.D.-IX rats	BT4C	Single intracranial administration of 100 μg of DRz4 with 5 μL of saline	Enhancement of survivability of tested animals	[101]
LMP1	DZ509	Balb/c nude mice	C666-1	When tumor size reached 5-8 mm, intratumoral administration of 33 μg of DZ509 once per day for a week	Suppression of tumor growth	[117]
	Dz1	Athymic Balb/c nude mice	CNE1-LMP1	When the tumor volume reached 60-100 mm^3, intratumoral administration of 20 μL of Dz1 with 1 μL of FuGENE6 twice a week	Suppression of tumor growth and radiosensitization	[126]
	Dz1	Athymic Balb/c nude mice	CNE1-LMP1	When the tumor volume reached 60-100 mm^3, intratumoral administration of 100 μg of Dz1 with 3 μL of FuGENE6 once every three days	Suppression of tumor growth and radiosensitization	[132]