Document Detail


Gene transfer to subdermal tissues via a new gene gun design.
MedLine Citation:
PMID:  12573061     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although particle-mediated gene transfer technology (gene gun) has been applied for gene transfer to external tissues, the application of this technology to other tissues has met with limited success. Here we report the development of a new design of a gene gun that uses helium discharge to propel DNA-coated gold beads that are suspended in liquid. Higher discharge pressures allow for the delivery of DNA to deeper tissues. Using the new gene gun to deliver a luciferase expression plasmid resulted in higher levels of gene expression in the skin than observed with conventional guns, as well as in subdermal tissues, including subcutaneous tumors. Even when using as little as 125 ng of DNA, gene expression in skin and muscle reached its peak level at 24 hr postbombardment and remained for at least 1 week. The use of a LacZ expression plasmid showed that gene expression was distributed throughout the skin with no observable pathology. The new gene gun was used to deliver a model tumor rejection antigen (a modified human papilloma virus [HPV] E7 gene) to mice. All of the treated animals developed protective immunity against HPV-positive tumors. These results demonstrate that our new design can be used in standard gene gun applications and extends the reach of gene gun technology to tissues that were previously unavailable.
Authors:
John Dileo; Theodore E Miller; Sophie Chesnoy; Leaf Huang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Human gene therapy     Volume:  14     ISSN:  1043-0342     ISO Abbreviation:  Hum. Gene Ther.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2003-02-07     Completed Date:  2003-07-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9008950     Medline TA:  Hum Gene Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  79-87     Citation Subset:  IM    
Affiliation:
Center for Pharmacogenetics and Department of Biochemistry and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biolistics / instrumentation*,  methods*
Cancer Vaccines / administration & dosage,  genetics
DNA / administration & dosage*
Dose-Response Relationship, Drug
Female
Gene Expression / drug effects
Gene Transfer Techniques / instrumentation*
Genes, Reporter
Helium
Injections, Intradermal
Luciferases / genetics
Mice
Mice, Inbred C57BL
Muscle, Skeletal / physiology
Oncogene Proteins, Viral / genetics,  immunology
Skin / metabolism
Subcutaneous Tissue / drug effects*,  metabolism*
beta-Galactosidase / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
CA74918/CA/NCI NIH HHS; CA82084/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cancer Vaccines; 0/Oncogene Proteins, Viral; 0/oncogene protein E7, Human papillomavirus type 16; 7440-59-7/Helium; 9007-49-2/DNA; EC 1.13.12.-/Luciferases; EC 3.2.1.23/beta-Galactosidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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