PMID- 11482983
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20071114
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 4
IP  - 2
DP  - 2001 Aug
TI  - Epstein-Barr virus/human vector provides high-level, long-term expression of 
      alpha1-antitrypsin in mice.
PG  - 122-9
AB  - We have constructed plasmid DNA vectors that contain Epstein-Barr virus (EBV) 
      sequences and the human gene (SERPINA1) encoding alpha1-Antitrypsin (AAT). We 
      demonstrate that a plasmid carrying the full SERPINA1 on a 19-kb genomic fragment 
      and the EBV gene EBNA1 and its family of repeats binding sites undergoes 
      efficient extrachromosomal replication in dividing mammalian tissue culture 
      cells. Therefore, use of a whole genomic therapeutic gene to provide both 
      replication and gene expression may be an effective gene therapy vector design, 
      if the target cells are dividing. The efficacy of this same vector for expression 
      of AAT in vivo in the nondividing cells of mouse liver was determined by 
      hydrodynamic injection of naked plasmid DNA by means of the tail vein. A single 
      injection of an EBV/genomic SERPINA1 vector provided >300 microg/ml of AAT, which 
      approached normal plasma levels and persisted for the >9-month duration of the 
      experiment. These data exceed most previously reported values, probably due to 
      sequences in the genomic DNA that resist silencing of gene expression, possibly 
      in combination with favorable effects on expression provided by the EBV 
      sequences. These results demonstrate that plasmid DNA with the correct cis-acting 
      sequences can provide in vivo long-term expression of protein at high levels that 
      are therapeutically relevant for gene therapy.
FAU - Stoll, S M
AU  - Stoll SM
AD  - Department of Genetics, Stanford University School of Medicine, Stanford, 
      California 94305, USA.
FAU - Sclimenti, C R
AU  - Sclimenti CR
FAU - Baba, E J
AU  - Baba EJ
FAU - Meuse, L
AU  - Meuse L
FAU - Kay, M A
AU  - Kay MA
FAU - Calos, M P
AU  - Calos MP
LA  - eng
GR  - DK49022/DK/NIDDK NIH HHS/United States
GR  - DK51834/DK/NIDDK NIH HHS/United States
GR  - HLL64274/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Trypsin Inhibitors)
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Animals
MH  - Blotting, Southern
MH  - Cell Line
MH  - DNA Replication/physiology
MH  - *Gene Transfer Techniques
MH  - *Genetic Vectors
MH  - Herpesvirus 4, Human/*genetics/metabolism
MH  - Humans
MH  - Liver/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Plasmids
MH  - Trypsin Inhibitors/biosynthesis/genetics
MH  - alpha 1-Antitrypsin/biosynthesis/*genetics
EDAT- 2001/08/03 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/08/03 10:00
PHST- 2001/08/03 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/08/03 10:00 [entrez]
AID - S1525-0016(01)90429-0 [pii]
AID - 10.1006/mthe.2001.0429 [doi]
PST - ppublish
SO  - Mol Ther. 2001 Aug;4(2):122-9. doi: 10.1006/mthe.2001.0429.