Robust and prolonged gene expression from injectable polymeric implants.
We introduce an injectable system for the formation of a biodegradable DNA-containing implant that releases DNA over a 2-month period to provide a robust and prolonged gene expression at the site. Sustained delivery of the appropriate plasmid DNA resulted in sustained expression of luciferase, the persistent appearance of secreted alkaline phosphatase in the serum and small blood vessel formation in the vicinity of the implant from the delivery of the development endothelial locus-1 gene. Local expression of development endothelial locus-1 protein promotes the development of blood vessels to meet the metabolic demands of new tissue and is a paradigm for the delivery of other growth factors that act locally to aid tissue regeneration. This delivery system involves simple preparation procedures and can be injected directly into the site, hence should be a useful approach to plasmid-based gene transfer for vaccination and tissue engineering.
Eliaz
R E
RE
Department of Biopharmaceutical Sciences and Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, CA 94143-0446, USA.
Szoka
F C
FC
D020341:Absorbable Implants; D000469:Alkaline Phosphatase; D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics; D015815:Cell Adhesion Molecules; D004247:DNA / Q000008:administration & dosage*; D058851:GPI-Linked Proteins; D015316:Genetic Therapy / Q000295:instrumentation* / Q000379:methods; D015552:Injections, Intralesional; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000235:genetics; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic; D011108:Polymers; D012867:Skin / Q000098:blood supply; D014162:Transfection / Q000379:methods
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491706:Edil3 protein, mouse; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D011108:Polymers; D004247:DNA; D008156:Luciferases; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental