Improving tissue survival; methods for enhancing organ transplant, musculocutaneous flap or skin graft survival by administering a nucleic acid sequence encoding hepatocyte growth factor; neovascularization; surgery; tissue-targeted therapy
Inventors
Kubo, Tateki • Tanag, Marvin A. • Yano, Kenji • Hosokawa, Ko • Morishita, Ryuichi
Assignees
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Publication Number
US-7790692-B2
Publication Date
2010-09-07
Expiration Date
Abstract
The present invention relates to the use of growth factors in improving tissue survival. In particular, the invention describes methods for enhancing organ transplant, musculocutaneous flap or skin graft survival by administering a nucleic acid sequence encoding hepatocyte growth factor.
Core Innovation
The invention relates to nucleic-acid encoding human hepatocyte growth factor (HGF) for use in decreasing necrosis of a flap or skin graft in a subject undergoing flap or skin graft surgery. The nucleic acid is provided as a vector comprising a nucleic acid sequence encoding human hepatocyte growth factor, and the vector is a plasmid comprising the nucleic acid sequence of SEQ ID NO:1 and the CMV promoter.
The method decreases necrosis by administering the vector prior to surgery, by injection at or near the planned site of the flap or skin graft. The plasmid vector is selected from pcDNA3.1(−) and pVAX1, and the described administration supports decreasing the area of necrosis in the flap or skin graft as compared to a subject who has not been injected with the vector.
The described tissue-supporting effect is associated with neovascularization / angiogenesis and enhanced flap or skin graft survival. Rat TRAM flap study results are described showing increased flap survival and higher laser Doppler-measured blood flow in animals treated with HGF versus saline or empty vector controls, with reduced necrosis and improved survival of flap or skin graft tissue.
Claims Coverage
The relevant material includes one independent claim focused on decreasing necrosis in flap or skin graft surgery. The independent claim requires administration prior to surgery by injection at or near the planned site, using a plasmid vector encoding human hepatocyte growth factor with specified sequence and promoter elements, and it requires that necrosis is decreased versus subjects not injected with the vector.
Decreasing necrosis of a flap or skin graft
A method for decreasing necrosis of a flap or skin graft in a subject undergoing flap or skin graft surgery, comprising administering prior to the surgery, by injection at or near the planned site, a vector comprising a nucleic acid sequence encoding human hepatocyte growth factor.
Plasmid vector for HGF expression with SEQ ID NO:1 and CMV promoter
The vector is a plasmid selected from the group consisting of pcDNA3.1(−) and pVAX1 and comprises the nucleic acid sequence of SEQ ID NO:1 and the CMV promoter.
Necrosis decrease versus non-injected subject
The area of necrosis in the flap or skin graft is decreased as compared to a subject who has not been injected with said vector.
Across the inventive core, the claims require a pre-surgery, site-adjacent injection of a specified plasmid vector encoding human hepatocyte growth factor (SEQ ID NO:1) under the CMV promoter, resulting in decreased necrosis of a flap or skin graft relative to subjects not injected with the vector.
Stated Advantages
Decreased area of necrosis in the flap or skin graft compared to a subject who has not been injected with the vector.
Increased flap survival and higher blood flow (laser Doppler-measured) in HGF-treated animals versus saline/empty vector controls.
Documented Applications
Decreasing necrosis of a flap or skin graft in a subject undergoing flap or skin graft surgery by administering an HGF-encoding plasmid vector prior to surgery.
Rat TRAM flap study to assess flap survival and blood flow after treatment with HGF versus saline/empty vector controls.
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