ADT Exam 1

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  1. Different types of oligonucleotide based therapeutic agents
    • tranditional antisense oligonucleotides
    • nucleic acid analogs and mimics
    • RNAi and siRNA
    • Aptamers
  2. Antisense oligonucleotides
    • single stranded DNA or RNA that targets mRNA and binds to it complementarly
    • 15-20 nucleotides (min of 12-15)
    • chemically synthesized
  3. How does binding mRNA by an antisense oligonucleotide lead to inhibition of protein synthesis?
    • geometric hinderance
    • ribonuclease action
  4. Size of ASONs
    • lenght effects specificity of binding
    • min of 12-15 nucleotide bases for use in humans
    • max of 18 to 24
  5. Advantages of ASONs
    • prevent synthesis of harmful proteins
    • gene specific
  6. disadvantages of ASONs
    • in vivo stability
    • drug delivery and cellular uptake
  7. Nucleic acid analogs and mimitecs
    • integrate into phosphodiester backbone and prevent protein synthesis
    • vitravene for CMV
  8. How do modified ASONs affect the mechanism of action of antisense oligonucleotides?
    • modifications increase stability
    • decrease degredation
  9. advantages of modified ASONs
    • more chemically stable than traditional
    • equivalently selective
    • less charge so easier to deliver
  10. Disadvantages of modified ASONs
    most do not activate RNAase H (do not act catalytically)
  11. RNAi and siRNA
    use base pairing to bind mRNA and cleave it before translation into a protein
  12. Problem with RNAi and siRNA
    long ds-RNA initiates antiviral response (interferon)
  13. Aptamers
    • bind the target protein instead of mRNA
    • may bind or have enzymatic activity
    • 15-25 bases long
    • optimized by invitro selection
  14. 4 steps of aptamer syntheses (SELEX)
    • pool preparation
    • selection of binders
    • amplification
    • aptamer isolation
  15. Macugen
    • aptamer
    • anti VEGF
  16. Major problems for delivery of oligonucleotides
    • size
    • polarity
    • cell specificity
  17. Delivery methods
    • liposomal
    • polumeric
    • peptide mediated
    • viral

Card Set Information

ADT Exam 1
2011-10-11 02:55:05
Oligonucleotide Based Therapeutics

Oligonucleotide Based Therapeutics
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