PMID- 9349425
OWN - NLM
STAT- MEDLINE
DCOM- 19971120
LR  - 20161124
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 4
IP  - 9
DP  - 1997 Sep
TI  - In vivo gene transfer via intravenous administration of cationic 
      lipid-protamine-DNA (LPD) complexes.
PG  - 891-900
AB  - A novel LPD formulation has been developed for in vivo gene transfer. It involves 
      the interaction of plasmid DNA with protamine sulfate, a cationic polypeptide, 
      followed by the addition of DOTAP cationic liposomes. Compared with DOTAP/DNA 
      complexes, LPD offers better protection of plasmid DNA against enzymatic 
      digestion and gives consistently higher gene expression in mice via tail vein 
      injection. When a luciferase reporter gene was employed, gene expression was 
      found in all tissues examined including lung, heart, spleen, liver and kidney 
      with the highest expression in the lung. The in vivo efficiency of LPD was 
      dependent upon charge ratio and was also affected by the lipid used. Increasing 
      the amount of DNA delivered induced an increase in gene expression. The optimal 
      dose was approximately 50 micrograms per mouse at which concentration 
      approximately 20 ng luciferase protein per milligram extracted tissue protein 
      could be detected in the lung. Increasing the DNA to 100 micrograms per mouse 
      resulted in toxicity and death of the animal. Gene expression in the lung was 
      detected as early as 1 h after injection, peaked at 6 h and declined thereafter. 
      High expression was also found in the spleen 6 h after injection but dropped very 
      rapidly thereafter. The in vivo gene expression by LPD was dependent upon the 
      route of administration since intraportal injection of LPD led to about a 
      100-fold decrease in gene expression in the lung as compared with i.v. injection. 
      Using lacZ as a reporter gene, it was shown that endothelial cells were the 
      primary locus of transgene expression in both the lung and spleen. No sign of 
      inflammation in these organs was noticed. Since protamine sulfate has been proven 
      to be nontoxic and only weakly immunogenic in humans, this novel vector may be 
      useful for clinical gene therapy.
FAU - Li, S
AU  - Li S
AD  - Department of Pharmacology, University of Pittsburgh School of Medicine, PA 
      15261, USA.
FAU - Huang, L
AU  - Huang L
LA  - eng
GR  - CA 59327/CA/NCI NIH HHS/United States
GR  - CA 64654/CA/NCI NIH HHS/United States
GR  - DK 44935/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Cations)
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Liposomes)
RN  - 0 (Protamines)
RN  - 0 (Quaternary Ammonium Compounds)
RN  - 9007-49-2 (DNA)
RN  - EC 1.13.12.- (Luciferases)
RN  - MR86K0XRQP (1,2-dioleoyloxy-3-(trimethylammonium)propane)
SB  - IM
MH  - Animals
MH  - Cations
MH  - *DNA
MH  - *Fatty Acids, Monounsaturated
MH  - Female
MH  - Fluorescent Dyes
MH  - Gene Expression
MH  - *Gene Transfer Techniques
MH  - *Genetic Vectors
MH  - Injections, Intravenous
MH  - Lac Operon
MH  - *Liposomes
MH  - Luciferases/genetics
MH  - Lung
MH  - Mice
MH  - Mice, Inbred Strains
MH  - *Protamines
MH  - *Quaternary Ammonium Compounds
EDAT- 1998/02/12 00:00
MHDA- 1998/02/12 00:01
CRDT- 1998/02/12 00:00
PHST- 1998/02/12 00:00 [pubmed]
PHST- 1998/02/12 00:01 [medline]
PHST- 1998/02/12 00:00 [entrez]
AID - 10.1038/sj.gt.3300482 [doi]
PST - ppublish
SO  - Gene Ther. 1997 Sep;4(9):891-900. doi: 10.1038/sj.gt.3300482.