Mod4 Research Proposal

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Contents

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.

Background Information

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.

Project Details and Methods

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.

References

  • Yacoby, I, et al. "Targeting antibacterial agents by using drug-carrying filamentous bacteriophages." Antimicrobial Agents and Chemotherapy 50.6(June 2006): 2087-2097.

This study used a method similar to our proposal, but with modified bacteriophages delivering antibiotics to target bacteria.

  • Jung J, et al. "Bio-nanocapsules for In vivo Pinpoint Drug Delivery." Yakugaku Zasshi 127.5(May 2007): 797-805.

This study uses a recombinant yeast-derived hepatitis B virus surface antigen particle as a hepatitis B vaccine, but the particle can incorporate other types of materials as well.

  • Lu, S, et al. "Gene Therapy for Ovarian Cancer Using Adenovirus-Mediated Transfer of Cytosine Deaminase Gene and Uracil Phosphoribosyltransferase Gene Directed by MDR1 Promoter." Cancer Biology Therapy 6.3(March 2007).

This study used an adenovirus to deliver gene therapy to ovarian cancer cells. While we wish to use drug treatment instead, this virus as a vector for delivery is promising.

  • Maatta, A. M., et al. "Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models." International Journal of Cancer."

This study examined the success of utilizing the Semliki Forest Virus to treat mouse tumor models. The results were very good, as tumor growth rate drastically decreased.

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