PMID- 25449800
OWN - NLM
STAT- MEDLINE
DCOM- 20150904
LR  - 20141220
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 197
DP  - 2015 Jan 10
TI  - Intrathecal injection of a therapeutic gene-containing polyplex to treat spinal 
      cord injury.
PG  - 1-9
LID - S0168-3659(14)00730-5 [pii]
LID - 10.1016/j.jconrel.2014.10.027 [doi]
AB  - Spinal cord injury (SCI) is a serious clinical problem that suddenly deprives 
      patients of neurologic function and drastically diminishes their quality of life. 
      Gene introduction has the potential to be effective for various pathological 
      states of SCI because various proteins can be produced just by modifying nucleic 
      acid sequences. In addition, the sustainable protein expression allows to 
      maintain its concentration at an effective level at the target site in the spinal 
      cord. Here we propose an approach using a polyplex system composed of plasmid DNA 
      (pDNA) and a cationic polymer, 
      polyN'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide [PAsp(DET)], that has high 
      capacity to promote endosome escape and the long-term safety by 
      self-catalytically degrading within a few days. We applied brain-derived 
      neurotrophic factor (BDNF)-expressing pDNA for SCI treatment by intrathecal 
      injection of PAsp(DET)/pDNA polyplex. A single administration of polyplex for 
      experimental SCI provided sufficient therapeutic effects including prevention of 
      neural cell death and enhancement of motor function recovery. This lasted for a 
      few weeks after SCI, demonstrating the capability of this system to express BDNF 
      in a safe and responsible manner for treatment of various pathological states in 
      SCI.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Hayakawa, Kentaro
AU  - Hayakawa K
AD  - Department of Rehabilitation for the Movement Functions, Research Institute, 
      National Rehabilitation Center for the Persons with Disabilities, Saitama, Japan; 
      Sensory and Motor System Medicine, Faculty of Medicine, The University of Tokyo, 
      Tokyo, Japan.
FAU - Uchida, Satoshi
AU  - Uchida S
AD  - Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative 
      Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
FAU - Ogata, Toru
AU  - Ogata T
AD  - Department of Rehabilitation for the Movement Functions, Research Institute, 
      National Rehabilitation Center for the Persons with Disabilities, Saitama, Japan.
FAU - Tanaka, Sakae
AU  - Tanaka S
AD  - Sensory and Motor System Medicine, Faculty of Medicine, The University of Tokyo, 
      Tokyo, Japan.
FAU - Kataoka, Kazunori
AU  - Kataoka K
AD  - Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative 
      Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 
      Department of Materials Engineering, Graduate School of Engineering, The 
      University of Tokyo, Tokyo, Japan. Electronic address: 
      kataoka@bmw.t.u-tokyo.ac.jp.
FAU - Itaka, Keiji
AU  - Itaka K
AD  - Sensory and Motor System Medicine, Faculty of Medicine, The University of Tokyo, 
      Tokyo, Japan; Laboratory of Clinical Biotechnology, Center for Disease Biology 
      and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 
      Tokyo, Japan. Electronic address: itaka-ort@umin.net.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141104
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytokines)
RN  - 0 (PAsp(DET))
RN  - 0 (Peptides)
RN  - 0 (Polymers)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Behavior, Animal
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cytokines/genetics
MH  - DNA/*administration & dosage
MH  - Female
MH  - Gene Transfer Techniques
MH  - Injections, Spinal
MH  - Mice, Inbred C57BL
MH  - Peptides/*administration & dosage
MH  - Plasmids
MH  - Polymers/*administration & dosage
MH  - Spinal Cord Injuries/genetics/physiopathology/*therapy
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor (BDNF)
OT  - Gene delivery
OT  - Intrathecal injection
OT  - Polyplex
OT  - Spinal cord injury
EDAT- 2014/12/03 06:00
MHDA- 2015/09/05 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/06/11 00:00 [received]
PHST- 2014/09/20 00:00 [revised]
PHST- 2014/10/27 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/09/05 06:00 [medline]
AID - S0168-3659(14)00730-5 [pii]
AID - 10.1016/j.jconrel.2014.10.027 [doi]
PST - ppublish
SO  - J Control Release. 2015 Jan 10;197:1-9. doi: 10.1016/j.jconrel.2014.10.027. Epub 
      2014 Nov 4.