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

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.

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.

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

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.

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.

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.

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?

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

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

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.

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