In-vivo particle mediated delivery of mRNA to mammalian tissues: ballistic and biologic effects

Biolistic transmission of mRNA provides transient gene therapy to in vivo organs. This study documents particle mediated mRNA transmission to a solid organ and wound healing model using the mRNA of Green Fluorescent Protein to determine optimal delivery parameters. Renal function, bullet penetration...

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Veröffentlicht in:Wound repair and regeneration 2001-07, Vol.9 (4), p.287-296
Hauptverfasser: Sohn, Richard L., Murray, Mary T., Schwarz, Karl, Nyitray, Joseph, Purray, Praveen, Franko, Alexander P., Palmer, Kenneth C., Diebel, Lawrence N., Dulchavsky, Scott A.
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container_end_page 296
container_issue 4
container_start_page 287
container_title Wound repair and regeneration
container_volume 9
creator Sohn, Richard L.
Murray, Mary T.
Schwarz, Karl
Nyitray, Joseph
Purray, Praveen
Franko, Alexander P.
Palmer, Kenneth C.
Diebel, Lawrence N.
Dulchavsky, Scott A.
description Biolistic transmission of mRNA provides transient gene therapy to in vivo organs. This study documents particle mediated mRNA transmission to a solid organ and wound healing model using the mRNA of Green Fluorescent Protein to determine optimal delivery parameters. Renal function, bullet penetration, cellular injury, and Green Fluorescent Protein synthesis were quantified. Chimeric human epidermal growth factor‐FLAG epitope cDNA or mRNA was transmitted to wounds in normal or steroid treated animals. Wound bursting strength, human epidermal growth factor‐FLAG, and collagen synthesis were determined. Injury and bullet penetration correlated with the delivery velocity and bullet size. Optimal delivery parameters were established which provided widespread Green Fluorescent Protein synthesis. Human epidermal growth factor‐FLAG treatment significantly increased collagen content and wound breaking strength in normal and steroid treated animals. FLAG protein synthesis was evident in mRNA treated fascia following treatment. We found the gene gun provides a novel method for efficient, in vivo delivery of mRNA‐based therapeutic strategies to mammalian organs with minimal histologic damage allowing transient expression of protein in in vivo target tissues. Co‐delivery of Green Fluorescent Protein mRNA may provide a useful positive control to determine effective transmission. Biolistic transmission of human epidermal growth factor‐FLAG mRNA provides increased tissue epidermal growth factor levels and accelerates wound healing in normal and steroid exposed animals.
doi_str_mv 10.1046/j.1524-475X.2001.00287.x
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This study documents particle mediated mRNA transmission to a solid organ and wound healing model using the mRNA of Green Fluorescent Protein to determine optimal delivery parameters. Renal function, bullet penetration, cellular injury, and Green Fluorescent Protein synthesis were quantified. Chimeric human epidermal growth factor‐FLAG epitope cDNA or mRNA was transmitted to wounds in normal or steroid treated animals. Wound bursting strength, human epidermal growth factor‐FLAG, and collagen synthesis were determined. Injury and bullet penetration correlated with the delivery velocity and bullet size. Optimal delivery parameters were established which provided widespread Green Fluorescent Protein synthesis. Human epidermal growth factor‐FLAG treatment significantly increased collagen content and wound breaking strength in normal and steroid treated animals. FLAG protein synthesis was evident in mRNA treated fascia following treatment. 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source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Animals
Biological Availability
Disease Models, Animal
Drug Delivery Systems
Epidermal Growth Factor - pharmacology
Gene Transfer Techniques
Genetic Therapy - methods
Green Fluorescent Proteins
Humans
Immunohistochemistry
Kidney - physiology
Luminescent Proteins
Male
Rats
Rats, Sprague-Dawley
Regeneration
RNA, Messenger - pharmacology
Sensitivity and Specificity
Wound Healing - physiology
Wounds and Injuries - genetics
Wounds and Injuries - pathology
Wounds and Injuries - therapy
title In-vivo particle mediated delivery of mRNA to mammalian tissues: ballistic and biologic effects
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