Expression vector pCK and therapeutic gene HGF

1. Development of pCK vector
Lee et al., Improved expression of vascular endothelial growth factor by naked DNA in mouse skeletal muscles: implication for gene therapy of ischemic diseases. Biochemical and Biophysical Research Communications, 2000;272:230-235

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2. Development and characterization of HGF-X7 in PAD model
Pyun et al., Naked DNA expressing two isoforms of hepatocyte growth factor induces collateral artery augmentation in a rabbit model of limb ischemia. Gene Therapy, 2010;17:1442-1452.

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Preclinical

3. Efficacy testing in CAD model
Carlsson et al., Quantitative MR measurements of regional and global left ventricular function and strain after intramyocardial transfer of VM202 into infarcted swine myocardium. American Journal of Physiology - Heart and Circulatory Physiology, 2008;295(2):H522-H532.

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Cho et al., Therapeutic angiogenesis using naked DNA expressing two isoforms of the hepatocyte growth factor in a porcine acute myocardial infarction model. European Journal of Cardio-Thoracic Surgery, 2008;34:857-863.

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Saeed et al., MR assessment of myocardial perfusion, viability, and function after intramyocardial transfer of VM202, a new plasmid human hepatocyte growth factor in ischemic swine myocardium. Radiology, 2008;249:107-118.

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Saeed et al., Cardiovascular magnetic resonance imaging in delivering and evaluating the efficacy of hepatocyte growth factor gene in chronic infarct scar. Cardiovascular Revascularization Medicine, 2011;12:111-122.

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Perin et al., Human hepatocyte growth factor (VM202) gene therapy via transendocardial injection in a pig model of chronic myocardial ischemia. Journal of Cardiac Failure, 2011;17:601-611.

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Hahn et al., Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte growth factor from naked plasmid DNA in a rat ischemic heart disease model. The Journal of Gene Medicine, 2011;13:549-555.

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4. Efficacy testing in neuropathic pain model
Nho et al., Effective control of neuropathic pain by transient expression of hepatocyte growth factor in a mouse chronic constriction injury model. The FASEB Journal, 2018; 32(9): 5119–5131.

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5. Regenerative effects in peripheral nerves
Ko et al., Hepatocyte growth factor (HGF) promotes peripheral nerve regeneration by activating repair Schwann cells. Scientific Reports, 2018;8(1):8316.

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Ko et al., c-Fos is necessary for HGF-mediated gene regulation and cell migration in Schwann cells. Biochemical and Biophysical Research Communications, 2018; 503(4):2855-2860.

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6. Muscle atrophy amelioration
Choi et al., Hepatocyte growth factor regulates the miR-206-HDAC4 cascade to control neurogenic muscle atrophy following surgical denervation in mice. Molecular Therapy-Nucleic Acids, 2018; 12;568-577.

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7. Bell-shaped dose response
Lee et al., Disproportionately high levels of HGF induce the degradation of the c-met receptor through the proteasomal degradation pathway, Biochemical and Biophysical Research Communications, 2018;505(3):925-930

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Clinical

1. VM202-PAD (Critical Limb Ischemia) Phase I US
Henry et al., Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: a phase I study. Gene Therapy, 2011;18:788-794.

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2. VM202-PAD (Critical Limb Ischemia) Phase I China
Gu et al., A phase I clinical study of naked DNA expressing two isoforms of hepatocyte growth factor to treat patients with critical limb ischemia. The Journal of Gene Medicine, 2011;13:602-610.

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3. VM202-CAD (Ischemic Heart Disease) Phase I Korea
Kim et al., Intramyocardial transfer of hepatocyte growth factor as an adjunct to CABG: phase I clinical study. Gene Therapy, 2013;20:717-722.

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4. VM202-DPN (Diabetic Peripheral Neuropathy) Phase I/II US
Ajroud-Driss et al., Phase 1/2 open-label dose-escalation study of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with painful diabetic neuropathy. Molecular Therapy, 2013;21:1279-1286.

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5. VM202-DPN (Diabetic Peripheral Neuropathy) Phase II US
Kessler et al., Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy. Annals of Clinical and Translational Neurology, 2015;2:465-478.

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6. VM202-PAD (Critical Limb Ischemia) Phase II US
Kibbe et al., Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia. Gene Therapy, 2016;23:306-312.

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7. VM202-ALS (Amyotrophic Lateral Sclerosis) Phase I US
Robert L. Sufit et al., Open label study to assess the safety of VM202 in subjects with amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2017 May;18(3-4):269-278.

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