Document Detail


In vivo analysis of intramuscular gene transfer in human subjects studied by on-line ultrasound imaging.
MedLine Citation:
PMID:  11506696     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The current study was designed to test the hypothesis that intramuscular (i.m.) injection of naked DNA leads to distribution of the injectate remote from the site of needle placement, a finding that might be expected to facilitate i.m. gene transfer. Transcutaneous ultrasound imaging was employed to monitor online the extent to which a solution of phVEGF165 was distributed among the skeletal musculature during 288 i.m. injections in 18 consecutive patients. In 237 (82.3%) of 288 muscle sites, the injection was performed into the distal calf muscle. In 51 (17.7%) of 288 muscle sites, injection was performed into the first and/or second interosseous muscles of the dorsal foot. Unperturbed muscle was recognized by a characteristic echogenic, stippled texture that was bounded by more intensely echogenic fascia. When i.m. gene transfer was performed into the calf muscles, the injectate was distributed along a longitudinal dimension of 3.59 +/- 0.79 cm (1.39-5.87 cm); the corresponding area of injectate measured by on-line planimetry was 1.83 +/- 0.51 cm2 (0.62-3.41 cm2). When i.m. gene transfer was performed into the interosseous muscles of the foot, the longitudinal extent of injectate distribution was 2.49 +/- 0.66 cm (1.61-3.91 cm), with a corresponding injectate area of 1.71 +/- 0.54 cm2 (0.51-2.86 cm2). These findings establish that a solution of plasmid DNA administered by direct i.m. injection into the skeletal muscles of the limb is distributed well beyond the site of needle entry. Thus, the use of multiple injections performed at different sites is likely to result in broad distribution of DNA injectate, a physical factor that may act to facilitate naked DNA and/or other gene transfer strategies.
Authors:
G Rauh; A Pieczek; W Irwin; R Schainfeld; J M Isner
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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:  12     ISSN:  1043-0342     ISO Abbreviation:  Hum. Gene Ther.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-16     Completed Date:  2001-11-01     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:  1543-9     Citation Subset:  IM    
Affiliation:
Shaughnessy Center for Clinical Genetics, Department of Medicine, Vascular Medicine, St. Elizabeth's Medical Center, Tuft's University School of Medicine, Boston, MA 02135, USA.
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MeSH Terms
Descriptor/Qualifier:
DNA / administration & dosage*,  metabolism*
Endothelial Growth Factors / genetics
Extremities / blood supply*
Gene Therapy / methods
Gene Transfer Techniques*
Humans
Ischemia / therapy*
Leg / ultrasonography
Lymphokines / genetics
Muscle, Skeletal / metabolism,  ultrasonography
Muscles / metabolism*,  ultrasonography*
Plasmids / administration & dosage,  metabolism
Time Factors
Ultrasonics*
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Grant Support
ID/Acronym/Agency:
HL53354/HL/NHLBI NIH HHS; HL57516/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Endothelial Growth Factors; 0/Lymphokines; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; 9007-49-2/DNA

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


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