1. Naked DNA By Amber Spiering, Amit Khosla, Jason Powell, Liz Viola, Dan Poor, Lisa Smith

2. What is ‘naked DNA’? Naked DNA can be used as a gene therapy for preventive and therapeutic vaccines DNA not attached to another molecule or encapsulated by a liposome or virus is referred to as naked DNA The proteins are not expressed Uses in arthritis, cancer, skin disease

3. How does Naked DNA work? The gene of interest is inserted into a DNA plasmid (highly stable, circular shape) that also contains short regulatory sequences The naked DNA plasmid is injected directly into muscle tissue The muscle tissue expresses the protein for a desired amount of time, stimulating the desired therapeutic response (immune response, inhibition of metastasis) Muscle cells are especially good for this technique because they are large cells that are multi-nucleated

4. Benefits of Naked DNA Broad Applicability Convenience Safety Ease of Manufacturing Cost effectiveness

5. Risks Unknown risks of naked DNA once it reaches the environment. –What happens if this form of gene transfer crosses over to other species? –What if the antibiotic resistant gene, that is used as a marker, leaks out of the gene?

6. The Naked DNA Company Vical, Inc currently holds all patents involving naked DNA technology “Leuvectin TM is a DNA/lipid complex containing the gene encoding IL-2, a cytokine that plays a role in stimulating immune response. Systemic IL-2 protein therapy is currently the only immunotherapeutic agent approved by the FDA for treatment of metastatic renal cell carcinoma, but its administration is associated with serious toxicity in the majority of patients. We expect that Leuvectin TM, when injected into tumors, will cause the malignant cells to produce IL-2. Local expression of IL-2 may then stimulate the patient's immune system to attack and destroy the tumor cells. Because Leuvectin TM delivers IL-2 locally rather than throughout the body, it may provide efficacy comparable to the protein treatment with fewer side effects. Leuvectin TM is being tested in Phase II clinical trials for patients with prostate cancer.”