PMID- 26015979
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150527
LR  - 20201001
IS  - 2329-0501 (Print)
IS  - 2329-0501 (Electronic)
IS  - 2329-0501 (Linking)
VI  - 1
DP  - 2014
TI  - Developmental stage determines efficiency of gene transfer to muscle satellite 
      cells by in utero delivery of adeno-associated virus vector serotype 2/9.
PG  - 14040
LID - 10.1038/mtm.2014.40 [doi]
AB  - Efficient gene transfer to muscle stem cells (satellite cells) has not been 
      achieved despite broad transduction of skeletal muscle by systemically 
      administered adeno-associated virus serotype 2/9 (AAV-9) in mice. We hypothesized 
      that cellular migration during fetal development would make satellite cells 
      accessible for gene transfer following in utero intravascular injection. We 
      injected AAV-9 encoding green fluorescent protein (GFP) marker gene into the 
      vascular space of mice ranging in ages from post-coital day 12 (E12) to postnatal 
      day 1 (P1). Satellite cell transduction was examined using: immunohistochemistry 
      and confocal microscopy, satellite cell migration assay, myofiber isolation and 
      FACS analysis. GFP positive myofibers were detected in all mature skeletal muscle 
      groups and up to 100% of the myofibers were transduced. We saw gestational 
      variation in cardiac and skeletal muscle expression. E16 injection resulted in 
      27.7 +/- 10.0% expression in satellite cells, which coincides with the timing of 
      satellite cell migration, and poor satellite cell expression before and after 
      satellite cell migration (E12 and P1). Our results demonstrate that efficient 
      gene expression is achieved in differentiated myofibers and satellite cells after 
      injection of AAV-9 in utero. These findings support the potential of prenatal 
      gene transfer for muscle based treatment strategies.
FAU - Stitelman, David H
AU  - Stitelman DH
AD  - The Children's Center for Fetal Research, Children's Hospital of Philadelphia , 
      Philadelphia, Pennsylvania, USA ; Department of Pediatric Surgery, Yale School of 
      Medicine , New Haven, Connecticut, USA.
FAU - Brazelton, Tim
AU  - Brazelton T
AD  - The Children's Center for Fetal Research, Children's Hospital of Philadelphia , 
      Philadelphia, Pennsylvania, USA.
FAU - Bora, Archana
AU  - Bora A
AD  - The Children's Center for Fetal Research, Children's Hospital of Philadelphia , 
      Philadelphia, Pennsylvania, USA.
FAU - Traas, Jeremy
AU  - Traas J
AD  - The Children's Center for Fetal Research, Children's Hospital of Philadelphia , 
      Philadelphia, Pennsylvania, USA.
FAU - Merianos, Demetri
AU  - Merianos D
AD  - The Children's Center for Fetal Research, Children's Hospital of Philadelphia , 
      Philadelphia, Pennsylvania, USA.
FAU - Limberis, Maria
AU  - Limberis M
AD  - Department of Pathology and Laboratory Medicine, Gene Therapy Program, Perelman 
      School of Medicine at the University of Pennsylvania , Philadelphia, 
      Pennsylvania, USA.
FAU - Davey, Marcus
AU  - Davey M
AD  - The Children's Center for Fetal Research, Children's Hospital of Philadelphia , 
      Philadelphia, Pennsylvania, USA.
FAU - Flake, Alan W
AU  - Flake AW
AD  - The Children's Center for Fetal Research, Children's Hospital of Philadelphia , 
      Philadelphia, Pennsylvania, USA.
LA  - eng
PT  - Journal Article
DEP - 20140910
PL  - United States
TA  - Mol Ther Methods Clin Dev
JT  - Molecular therapy. Methods & clinical development
JID - 101624857
PMC - PMC4362369
EDAT- 2014/01/01 00:00
MHDA- 2014/01/01 00:01
PMCR- 2014/09/10
CRDT- 2015/05/28 06:00
PHST- 2014/04/10 00:00 [received]
PHST- 2014/06/19 00:00 [revised]
PHST- 2014/07/28 00:00 [accepted]
PHST- 2015/05/28 06:00 [entrez]
PHST- 2014/01/01 00:00 [pubmed]
PHST- 2014/01/01 00:01 [medline]
PHST- 2014/09/10 00:00 [pmc-release]
AID - S2329-0501(16)30108-5 [pii]
AID - 10.1038/mtm.2014.40 [doi]
PST - epublish
SO  - Mol Ther Methods Clin Dev. 2014 Sep 10;1:14040. doi: 10.1038/mtm.2014.40. 
      eCollection 2014.