PMID- 22762556
OWN - NLM
STAT- MEDLINE
DCOM- 20130405
LR  - 20190907
IS  - 1873-4294 (Electronic)
IS  - 1568-0266 (Linking)
VI  - 12
IP  - 15
DP  - 2012
TI  - Modification of decoy oligodeoxynucleotides to achieve the stability and 
      therapeutic efficacy.
PG  - 1603-7
AB  - The decoy oligodeoxynucleotide (ODN) serves as a decoy sequence for a target 
      transcription factor, then inhibiting its binding to the authentic sequence at 
      the promoter, and consequently hinders the gene expression. ODNs should be 
      properly up taken by the cell and tissue, be specific for one nuclear factor, and 
      be stable against intracellular and serum nucleases. Since phosphodiester oligos 
      are easily degradated by nucleases, chemical modification such as 
      phosphorothioation, and structural modification by ligation of the extremities of 
      two single-strand phosphodiester sequence resulting in a dumbbell shaped ODN 
      (Ribbon-type decoy ODN) are performed to increase the stability of ODNs. In 
      combination, phosphorothioation of specific regions in Ribbon-type decoy has 
      further increased its stability, and the introduction of saturated hydrocarbon 
      polymer spacer linking the two double strands also improved the stability and 
      reduced the production cost. The cellular delivery has been optimized by using 
      the biodegradable polymer D,L-lactide-co-glycolide (PLGA) as a carrier to ODN. 
      The nuclear factor-kappa B (NF-kappaB) is a convergent point of different pathways, 
      with main role in many pathologies, and poses as an ideal target for decoy ODN 
      strategy. Following this we have designed ODN targeting NF-kappaB, and in this 
      review, we are going to discuss the various modification performed in an attempt 
      to improve the ODN efficacy, and some promising pre-clinical data and clinical 
      trials using NF-kappaB decoy ODN.
FAU - Osako, Mariana Kiomy
AU  - Osako MK
AD  - Division of Vascular Medicine and Epigenetics, United Graduate School of Child 
      Development, Osaka University, Osaka, Japan.
FAU - Nakagami, Hironori
AU  - Nakagami H
FAU - Morishita, Ryuichi
AU  - Morishita R
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Top Med Chem
JT  - Current topics in medicinal chemistry
JID - 101119673
RN  - 0 (Drug Carriers)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappaB decoy)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Phosphorothioate Oligonucleotides)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Clinical Trials as Topic
MH  - Drug Carriers/*chemistry
MH  - Drug Stability
MH  - Humans
MH  - Lactic Acid/*chemistry
MH  - Molecular Sequence Data
MH  - NF-kappa B/antagonists & inhibitors/genetics
MH  - *Oligodeoxyribonucleotides/chemistry/genetics/therapeutic use
MH  - *Phosphorothioate Oligonucleotides/chemistry/genetics/therapeutic use
MH  - Polyglycolic Acid/*chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Transcription, Genetic
EDAT- 2012/07/06 06:00
MHDA- 2013/04/06 06:00
CRDT- 2012/07/06 06:00
PHST- 2012/05/09 00:00 [received]
PHST- 2012/06/18 00:00 [accepted]
PHST- 2012/07/06 06:00 [entrez]
PHST- 2012/07/06 06:00 [pubmed]
PHST- 2013/04/06 06:00 [medline]
AID - CTMC-EPUB-20120702-3 [pii]
AID - 10.2174/156802612803531397 [doi]
PST - ppublish
SO  - Curr Top Med Chem. 2012;12(15):1603-7. doi: 10.2174/156802612803531397.