PMID- 29523880
OWN - NLM
STAT- MEDLINE
DCOM- 20181011
LR  - 20181011
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 25
IP  - 2
DP  - 2018 Apr
TI  - Widespread transduction of astrocytes and neurons in the mouse central nervous 
      system after systemic delivery of a self-complementary AAV-PHP.B vector.
PG  - 83-92
LID - 10.1038/s41434-018-0005-z [doi]
AB  - Until recently, adeno-associated virus 9 (AAV9) was considered the AAV serotype 
      most effective in crossing the blood-brain barrier (BBB) and transducing cells of 
      the central nervous system (CNS), following systemic injection. However, a newly 
      engineered capsid, AAV-PHP.B, is reported to cross the BBB at even higher 
      efficiency. We investigated how much we could boost CNS transgene expression by 
      using AAV-PHP.B carrying a self-complementary (sc) genome. To allow comparison, 6 
      weeks old C57BL/6 mice received intravenous injections of scAAV2/9-GFP or 
      scAAV2/PHP.B-GFP at equivalent doses. Three weeks postinjection, transgene 
      expression was assessed in brain and spinal cord. We consistently observed more 
      widespread CNS transduction and higher levels of transgene expression when using 
      the scAAV2/PHP.B-GFP vector. In particular, we observed an unprecedented level of 
      astrocyte transduction in the cortex, when using a ubiquitous CBA promoter. In 
      comparison, neuronal transduction was much lower than previously reported. 
      However, strong neuronal expression (including spinal motor neurons) was observed 
      when the human synapsin promoter was used. These findings constitute the first 
      reported use of an AAV-PHP.B capsid, encapsulating a scAAV genome, for gene 
      transfer in adult mice. Our results underscore the potential of this AAV 
      construct as a platform for safer and more efficacious gene therapy vectors for 
      the CNS.
FAU - Rincon, Melvin Y
AU  - Rincon MY
AD  - VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium.
AD  - KU Leuven, Department of Neuroscience, Leuven, Belgium.
FAU - de Vin, Filip
AU  - de Vin F
AD  - VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium.
AD  - KU Leuven, Department of Neuroscience, Leuven, Belgium.
FAU - Duque, Sandra I
AU  - Duque SI
AD  - VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium.
AD  - KU Leuven, Department of Neuroscience, Leuven, Belgium.
FAU - Fripont, Shelly
AU  - Fripont S
AD  - VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium.
AD  - KU Leuven, Department of Neuroscience, Leuven, Belgium.
FAU - Castaldo, Stephanie A
AU  - Castaldo SA
AD  - VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium.
AD  - KU Leuven, Department of Oncology, Leuven, Belgium.
FAU - Bouhuijzen-Wenger, Jessica
AU  - Bouhuijzen-Wenger J
AD  - VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium.
AD  - KU Leuven, Department of Neuroscience, Leuven, Belgium.
FAU - Holt, Matthew G
AU  - Holt MG
AD  - VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium. 
      Matthew.Holt@kuleuven.vib.be.
AD  - KU Leuven, Department of Neuroscience, Leuven, Belgium. 
      Matthew.Holt@kuleuven.vib.be.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180309
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Synapsins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Brain/cytology/*metabolism
MH  - Dependovirus/*genetics
MH  - Female
MH  - Genetic Vectors/*administration & dosage
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Humans
MH  - Mice, Inbred C57BL
MH  - Neurons/*metabolism
MH  - Promoter Regions, Genetic
MH  - Synapsins/genetics
MH  - *Transduction, Genetic
MH  - Transgenes
EDAT- 2018/03/11 06:00
MHDA- 2018/10/12 06:00
CRDT- 2018/03/11 06:00
PHST- 2017/06/28 00:00 [received]
PHST- 2018/01/30 00:00 [accepted]
PHST- 2018/01/23 00:00 [revised]
PHST- 2018/03/11 06:00 [pubmed]
PHST- 2018/10/12 06:00 [medline]
PHST- 2018/03/11 06:00 [entrez]
AID - 10.1038/s41434-018-0005-z [pii]
AID - 10.1038/s41434-018-0005-z [doi]
PST - ppublish
SO  - Gene Ther. 2018 Apr;25(2):83-92. doi: 10.1038/s41434-018-0005-z. Epub 2018 Mar 9.