From 2012.igem.org

Latest revision as of 16:15, 26 October 2012

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  • 1. Introduction
  • 2. PnA System
  • 3. Virus-Like Particles
    • CCMV
    • HepB
    • Polerovirus Natural BioBrick
  • 4. Outside Modification
  • 5. Inside Modification
  • 6. Detection of VLPs
  • 7. Applications
  • 8. The Constructor
  • 9. Final Overview
• Human Practices
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  • 1. Mini Symposium
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  • 5. Munich CAS Conference
• Safety
  • Introduction
  • 1. General safety
  • 2. Virus-related safety
  • 3. Regulations
  • 4. Safety suggestions
  • 5. Safety of applications
• Modeling
  • Human Body Model
  • Tertiary folding prediction
  • VLP assembly model
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Safety of medical application: A brief literature study

VLPs in the human body

Virus-Like Particles have been successfully used in human therapy, both as vaccines and as medical delivery vessels [1-4]. However, adverse effects such as flu-like symptoms or infusion reactions have also been reported [5].
In our theoretical case-study, we want to use our Hepatitis B VLP. In this year’s review by Yang et. al., the HepB VLP is described as "efficient and safe" [6]. Although the authors focus on its use in vaccines, they also describe how it could vaccinate for other pathogens than the virus it originates from, suggesting that the immune system could be fooled by this particle.
We think that our PnA System may be able to help prevent immune response problems by covering the particle in a stealth coating such as described by Carlisle et. Al. [7]

VLP-encapsulated medicine

Although the majority of literature on medical applications of VLPs focusses on their use as vaccines [1, 2, 8], there are also examples of studies with VLP-encapsulated medicine in humans [3, 4].
In our case-study, we focus on treatment of human colon cancer. Already in 2007, Ramqvist et. al. described the possibilities of treating different cancer variants using VLPs [9]. Today, the most mentioned medicines in the treatment of colon cancer are Irinotecan[10], oxaliplatin[11] and capecitabine [12]. We argue that any medicine can be packaged inside a VLP even if only due to assembly in presence of that medicine, and therefore treatment should be feasible.

References

1. Harro, C.D., et al., Safety and Immunogenicity Trial in Adult Volunteers of a Human Papillomavirus 16 L1 Virus-Like Particle Vaccine. Journal of the National Cancer Institute, 2001. 93(4): p. 284-292.

2. Roy, P. and R. Noad, Virus-like particles as a vaccine delivery system - Myths and facts. Human Vaccines, 2008. 4(1): p. 5-12.

3. Ma, Y., R.J.M. Nolte, and J.J.L.M. Cornelissen, Virus-based nanocarriers for drug delivery. Advanced Drug Delivery Reviews, 2012. 64(9): p. 811-825.

4. Garcea, R.L. and L. Gissmann, Virus-like particles as vaccines and vessels for the delivery of small molecules. Current Opinion in Biotechnology, 2004. 15(6): p. 513-517.

5. Lorence, R.M., et al., Phase 1 Clinical Experience Using Intravenous Administration of PV701, an Oncolytic Newcastle Disease Virus. Current Cancer Drug Targets, 2007. 7(2): p. 157-167.

6. Yang, X.-Y., H. Bo, and Y.-L. Shu, Hepatitis B virus core antigen as a carrier for virus-like partical vaccine: a review. Bing du xue bao = Chinese journal of virology / [bian ji, Bing du xue bao bian ji wei yuan hui], 2012. 28(3): p. 311-6.

7. Carlisle, R.C., et al., Coating of adeno-associated virus with reactive polymers can ablate virus tropism, enable retargeting and provide resistance to neutralising antisera. The Journal of Gene Medicine, 2008. 10(4): p. 400-411.

8. Roldao, A., et al., Virus-like particles in vaccine development. Expert Review of Vaccines, 2010. 9(10): p. 1149-1176.

9. Ramqvist, T., K. Andreasson, and T. Dalianis, Vaccination, immune and gene therapy based on virus-like particles against viral infections and cancer. Expert Opinion on Biological Therapy, 2007. 7(7): p. 997-1007.

10. de Jonge, H., M. Naesens, and D.R. Kuypers, New insights into the pharmacokinetics and pharmacodynamics of the calcineurin inhibitors and mycophenolic acid: possible consequences for therapeutic drug monitoring in solid organ transplantation. Ther Drug Monit, 2009. 31(4): p. 416-35.

11. Takimoto, C.H., et al., Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function. Clin Cancer Res, 2007. 13(16): p. 4832-9.

12. Blesch, K.S., et al., Clinical pharmacokinetic/pharmacodynamic and physiologically based pharmacokinetic modeling in new drug development: the capecitabine experience. Invest New Drugs, 2003. 21(2): p. 195-223.

Safety

Introduction

1. General safety

2. Virus-related safety

3. Regulations

4. Suggestions

5. Safety of application