1. Mark Fang Stanford iGEM 08-09
Tinkering with the Biochemistry of Life: Viruses, Prions, and Peptide Nucleic Acids
Mark Fang
Stanford iGEM 08-09

2. Peptide Nucleic Acid
Peptide nucleic acid (PNA) is an artificial polymer that resembles DNA and RNA.
Like DNA, PNA has sequences of nucleic acid bases, but backbone is composed of glycine amino acid residues and ethyl amine units, instead of ribose and phosphate.

3. PNA Important characteristics:
Exhibits Watson-Crick base pairing and forms double helices with other PNA, DNA, and RNA
Binds more strongly to DNA and RNA
Is not easily recognized by proteases and nucleases (resists enzymatic degradation)
Overall, PNA is much more stable than DNA and RNA.

4. Virus
Viruses have two or three parts:
Genetic material (DNA or RNA)
Protein coat
Lipid envelope
Both envelope and protein coat have protein receptors and display surface antigens that assist binding to cells

5. Prion Thought to be misfolded version of a normal protein Example:
Normal: PrP
Misfolded: PrPsc
PrPsc can cause normal PrP to misfold.
Accumulates, causes cell death and pathogenesis.

6. Antiviral Drugs Antiviral drug design: Identify viral protein targets
Determine which targets can be disabled
Design chemical that inhibits target
Similarly, body recognizes target protein antigens, mounts defense based on antigen recognition.

7. Antiviral Drugs
Problem: viruses can mutate and change surface antigens via antigenic shift, mutation, etc.
Result: body and antiviral drugs targeting these antigens no longer recognize virus.

8. Solution: Therapeutic Use of PNA
Take advantage of antigenic shift to incorporate PNA into pathogenic viruses.
PNA resistant to mutation/mismatch; lock viral antigen sequence -> inhibit antigen mutation?

9. PrPsc Diagnosis Problem: symptoms take long time to become apparent
Solution: amplify effect of PrPsc in affected individuals, quarantine

10. Prions and Viruses Engineer virus that can attack other viruses?
Mechanism: prion version of viral receptors that mutates normal receptors of pathogenically active viruses?

11. Viral Polymerization
Demonstrate that viruses can be engineered to exhibit receptors and antigens that will allow them to interact and bind to each other in polymers.

12. Other Applications of PNA
Stable data storage in cells?
Gene expression inhibition?