Tinkering with the Biochemistry of Life:

Viruses, Prions, and Peptide Nucleic AcidsMark Fang

Stanford iGEM 08-09

Peptide Nucleic AcidPeptide 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:1. Exhibits Watson-Crick base pairing and

forms double helices with other PNA, DNA, and RNA

2. Binds more strongly to DNA and RNA3. 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: PrPMisfolded: PrPsc

PrPsc can cause normal PrP to misfold.Accumulates, causes cell death and

pathogenesis.

Antiviral Drugs

Antiviral drug design:1. Identify viral protein targets2. Determine which targets can be disabled3. 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 PolymerizationDemonstrate 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?