21.06.2012 - Researchers have halted the growth of skin cancer with help of a DNA that acts like an enzyme
Dublin/New South Wales – A DNA-based enzyme can block the growth of two common types of skin cancer, basal cell carcinoma and squamous cell carcinoma, an Australian-Irish team of researchers has demonstrated (Science Translational Medicine, 20 June). Dubbed Dz13, the DNAzyme could potentially be a safe and effective therapy for skin cancer in humans.
In animal models for both skin cancers as well as metastasis, the molecule stopped tumour spread and growth effectively by binding to and destroying the RNA of a key gene called c-Jun. The proliferation–related transcription factor controlled cancer growth by suppression of neovascularisation and increasing apoptosis of tumour cells. Phenotypically, the DNAzyme reduced lung nodule formation and an intratumour injection of 100 µg Dz13 led to complete tumour remission after 35 days.
Levon Khachigian and colleagues, who have filed an US patent on „vascular therapeutics“, also found that Dz13 probably triggers an immune response to inhibit tumour growth because it acts better in immunocompetent than in immunocompromised mice. In GLP-compliant toxicology tests, the researchers proved in monkeys, pigs and rats that Dz13 is safe and well tolerated. It did not interfere in more than 70 physiological relevant bioassays, suggesting a reduced propensity for off-target effects.
The authors suggest to test the compound in first-in-man trails. Up to now DNAzymes have not caught on as therapeutic agents partly due to the fact that delivery has been a challenge for DNAzyme therapeutic applications. Now, the researchers have formulated their c-jun mRNA–targeted DNAzyme in complex with a DOTAP/DOPE–based lipid carrier.
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The LiposoFast-Basic produces unilamellar liposomes by the manual extrusion of a multilamellar liposome suspension through a polycarbonate membrane of defined pore size, using gas-tight, glass syringes. more