PMID- 25599855
OWN - NLM
STAT- MEDLINE
DCOM- 20151123
LR  - 20150216
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 201
DP  - 2015 Mar 10
TI  - Treatment of neurological disorders by introducing mRNA in vivo using polyplex 
      nanomicelles.
PG  - 41-8
LID - S0168-3659(15)00057-7 [pii]
LID - 10.1016/j.jconrel.2015.01.017 [doi]
AB  - Sensory nerve disorders are difficult to cure completely considering poor nerve 
      regeneration capacity and difficulties in accurately targeting neural tissues. 
      Administering mRNA is a promising approach for treating neurological disorders 
      because mRNA can provide proteins and peptides in their native forms for mature 
      non-dividing neural cells, without the need of entering their nuclei. However, 
      direct mRNA administration into neural tissues in vivo has been challenging due 
      to too unstable manner of mRNA and its strong immunogenicity. Thus, using a 
      suitable carrier is essential for effective mRNA administration. For this 
      purpose, we established a novel carrier based on the self-assembly of 
      polyethylene glycol (PEG)-polyamino acid block copolymer, i.e. polyplex 
      nanomicelles. To investigate the feasibility and efficacy of mRNA administration 
      for the treatment of sensory nerve disorders, we used a mouse model of 
      experimentally induced olfactory dysfunction. Intranasal administration of 
      mRNA-loaded nanomicelles provided an efficient and sustained protein expression 
      for nearly two days in nasal tissues, particularly in the lamina propria which 
      contains olfactory nerve fibers, with effectively regulating the immunogenicity 
      of mRNA. Consequently, once-daily intranasal administration of brain-derived 
      neurotrophic factor (BDNF)-expressing mRNA using polyplex nanomicelles remarkably 
      enhanced the neurological recovery of olfactory function along with repairing the 
      olfactory epithelium to a nearly normal architecture. To the best of our 
      knowledge, this is the first study to show the therapeutic potential of 
      introducing exogenous mRNA for the treatment of neurological disorders. These 
      results indicate the feasibility and safety of using mRNA, and provide a novel 
      strategy of mRNA-based therapy.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Baba, Miyuki
AU  - Baba M
AD  - Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative 
      Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, 
      Bunkyo-ku, Tokyo 113-0033, Japan; Department of Otolaryngology, Head and Neck 
      Surgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 
      Tokyo 113-8655, Japan.
FAU - Itaka, Keiji
AU  - Itaka K
AD  - Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative 
      Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, 
      Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: itaka-ort@umin.net.
FAU - Kondo, Kenji
AU  - Kondo K
AD  - Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, The 
      University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
FAU - Yamasoba, Tatsuya
AU  - Yamasoba T
AD  - Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, The 
      University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, 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, 7-3-1 Hongo, 
      Bunkyo-ku, Tokyo 113-0033, Japan; Department of Materials Engineering, Graduate 
      School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 
      113-8656, Japan. Electronic address: kataoka@bmw.t.u-tokyo.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150117
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 (Interleukin-6)
RN  - 0 (Micelles)
RN  - 0 (Olfactory Marker Protein)
RN  - 0 (Omp protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (interleukin-6, mouse)
RN  - 554Z48XN5E (Methimazole)
SB  - IM
MH  - Administration, Intranasal
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Gene Transfer Techniques
MH  - Interleukin-6/genetics
MH  - Methimazole
MH  - Mice, Inbred BALB C
MH  - *Micelles
MH  - Nanostructures/*administration & dosage
MH  - Olfaction Disorders/chemically induced/metabolism/pathology/*therapy
MH  - Olfactory Marker Protein/genetics
MH  - Olfactory Mucosa/drug effects/metabolism/pathology
MH  - RNA, Messenger/*administration & dosage
MH  - Tumor Necrosis Factor-alpha/genetics
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor (BDNF)
OT  - Messenger RNA (mRNA) administration
OT  - Neurological disorders
OT  - Olfactory dysfunction
OT  - mRNA-based therapy
EDAT- 2015/01/21 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/01/21 06:00
PHST- 2014/09/10 00:00 [received]
PHST- 2014/12/30 00:00 [revised]
PHST- 2015/01/16 00:00 [accepted]
PHST- 2015/01/21 06:00 [entrez]
PHST- 2015/01/21 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0168-3659(15)00057-7 [pii]
AID - 10.1016/j.jconrel.2015.01.017 [doi]
PST - ppublish
SO  - J Control Release. 2015 Mar 10;201:41-8. doi: 10.1016/j.jconrel.2015.01.017. Epub 
      2015 Jan 17.