Tinkering with the Biochemistry of Life: Viruses, Prions, and Peptide Nucleic Acids

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Tinkering with the Biochemistry of LifeViruses,
Prions, and Peptide Nucleic Acids

• Mark Fang
• Stanford iGEM 08-09

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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.

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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.

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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

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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.

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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.

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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.

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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 -gt inhibit antigen mutation?

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PrPsc Diagnosis

• Problem symptoms take long time to become
  apparent
• Solution amplify effect of PrPsc in affected
  individuals, quarantine

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Prions and Viruses

• Engineer virus that can attack other viruses?
• Mechanism prion version of viral receptors that
  mutates normal receptors of pathogenically active
  viruses?

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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.

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Other Applications of PNA

• Stable data storage in cells?
• Gene expression inhibition?