Mod4 Research Proposal

Project Overview
We propose a method of delivering cancer drugs, such as chemotherapy, through linkage to a virus. This virus would have a modified specificity so that it only infects cancerous mammalian cells.

Cancer

 * Cancer is one of the leading causes of death throughout the world.
 * A major obstacle is cancer treatment is the lack of specificity - drugs attack cancerous cells, but they attack healthy cells as well
 * Cancerous cells, such as tumors, are known to have modified surface proteins

Viruses

 * Huge variety - can infect all living things

Research Problem and Goals
We aim to create a viral vector to specifically deliver metal ions to tumor cells. We will use an adenovirus modified to bind EGF receptors, that contains metal ions cross-linked to the viral genetic material. If successful, this method will allow directed MRI analysis of cancer.

Modified Adenovirus

 * Ad5
 * Make virus replication - deficient
 * Attach EGF (epidermal growth factor) to modified CAR (coxsackievirus and adenovirus receptor) ligand (Dmitriev)
 * Cross-link metal ion (Au? Pt?) to viral DNA

JenniferWest Haalas Mirkin

Metal Ion Uptake

 * Test for success/ efficiency of metal ion integration into virus and ability to complex with DNA

Transfer into Tumor Cells in vitro

 * Culture human lung tumor cells and add viral vector
 * Examine success of injection of viral genetic material into cells
 * Measure metal concentration

Transfer into Tumor Cell in vivo

 * Create/ acquire mouse model of lung cancer
 * Inject viral vector into model
 * Test MRI specificity

Predicted Outcomes
If all goes well, our virus should be able to deliver metal ions specifically to cancerous tumor cells. We could detect this by also attaching GFP to the adenovirus, then detecting whether the virus showed specificity for cancerous cells.

Resources

 * model for cancer
 * altered adenovirus

Societal Impact
This method could be generalized to other types of cancer and perhaps other diseases as well, if they overexpress a certain type of receptor. If this turned out to be an effective way to treat cancer, then people diagnosed with cancer would have higher recovery rates.