Baumgartner, Iris; Chronos, Nicolas; Comerota, Anthony; Henry, Timothy; Pasquet, Jean-Paul; Finiels, François; Caron, Anne; Dedieu, Jean-François; Pilsudski, Richard; Delaère, Pia (2009). Local gene transfer and expression following intramuscular administration of FGF-1 plasmid DNA in patients with critical limb ischemia. Molecular therapy, 17(5), pp. 914-21. New York, N.Y.: Nature Publishing Group 10.1038/mt.2009.24
Full text not available from this repository.NV1FGF is an expression plasmid encoding sp.FGF-1(21-154) currently under investigation for therapeutic angiogenesis in clinical trials. NV1FGF plasmid distribution and transgene expression following intramuscular (IM) injection in patients is unknown. The study involved six patients with chronic critical limb ischemia (CLI) planned to undergo amputation. A total dose of 0.5, 2, or 4 mg NV1FGF was administered as eight IM injections (0.006, 0.25, or 0.5 mg per injection) 3-5 days before amputation. Injected sites (30 cm(3)) were divided into equally sized smaller pieces to assess spatial distribution of NV1FGF sequences (PCR), NV1FGF mRNA (reverse transcriptase-PCR), and fibroblast growth factor-1 (FGF-1)-expressing cells (immunohistochemistry). Data indicated gene expression at all doses. The distribution area was within 5-12 cm for NV1FGF sequences containing the expression cassette, up to 5 cm for NV1FGF mRNA, and up to 3 cm for FGF-1-expressing myofibers. All FGF receptors were detected indicating robust potential for bioactivity after NV1FGF gene transfer. Circulating levels of NV1FGF sequences were shown to decrease within days after injection. Data support demonstration of plasmid-mediated gene transfer and expression in muscles from patients with CLI. FGF-1 expression was shown to be limited to injection sites, which supports the concept of multiple-site injection for therapeutic use.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Angiology |
UniBE Contributor: |
Baumgartner, Iris |
ISSN: |
1525-0016 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:13 |
Last Modified: |
05 Dec 2022 14:22 |
Publisher DOI: |
10.1038/mt.2009.24 |
PubMed ID: |
19240689 |
Web of Science ID: |
000265640700026 |
URI: |
https://boris.unibe.ch/id/eprint/32071 (FactScience: 196939) |
Actions (login required)
 |
Edit item |