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

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:
1. Exhibits Watson-Crick base pairing and forms double
helices with other PNA, DNA, and RNA
2. Binds more strongly to DNA and RNA
3. 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:
1. Identify viral protein targets
2. Determine which targets can be disabled
3. 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?