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ADT Exam 1
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Different types of oligonucleotide based therapeutic agents
tranditional antisense oligonucleotides
nucleic acid analogs and mimics
RNAi and siRNA
Aptamers
Antisense oligonucleotides
single stranded DNA or RNA that targets mRNA and binds to it complementarly
15-20 nucleotides (min of 12-15)
chemically synthesized
How does binding mRNA by an antisense oligonucleotide lead to inhibition of protein synthesis?
geometric hinderance
ribonuclease action
Size of ASONs
lenght effects specificity of binding
min of 12-15 nucleotide bases for use in humans
max of 18 to 24
Advantages of ASONs
prevent synthesis of harmful proteins
gene specific
disadvantages of ASONs
in vivo stability
drug delivery and cellular uptake
Nucleic acid analogs and mimitecs
integrate into phosphodiester backbone and prevent protein synthesis
vitravene for CMV
How do modified ASONs affect the mechanism of action of antisense oligonucleotides?
modifications increase stability
decrease degredation
advantages of modified ASONs
more chemically stable than traditional
equivalently selective
less charge so easier to deliver
Disadvantages of modified ASONs
most do not activate RNAase H (do not act catalytically)
RNAi and siRNA
use base pairing to bind mRNA and cleave it before translation into a protein
Problem with RNAi and siRNA
long ds-RNA initiates antiviral response (interferon)
Aptamers
bind the target protein instead of mRNA
may bind or have enzymatic activity
15-25 bases long
optimized by invitro selection
4 steps of aptamer syntheses (SELEX)
pool preparation
selection of binders
amplification
aptamer isolation
Macugen
aptamer
anti VEGF
Major problems for delivery of oligonucleotides
size
polarity
cell specificity
Delivery methods
liposomal
polumeric
peptide mediated
viral
Author
Rx2013
ID
107960
Card Set
ADT Exam 1
Description
Oligonucleotide Based Therapeutics
Updated
2011-10-11T02:55:05Z
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