ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
IRES-based vector coexpressing FGF2 and Cyr61 provides synergistic and safe therapeutics of lower limb ischemia.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Platform-dependent performance of P2A and IRES linkers in multicistronic gene expression.Genes & genomics · 2026Article
- IRES-Mediated Translation: Expanding the Toolkits of RNA Therapy.International journal of molecular sciences · 2025Review
- Internal Ribosome Entry Site (IRES)-Mediated Translation and Its Potential for Novel mRNA-Based Therapy Development.Biomedicines · 2022Review
- Production and Application of Multicistronic Constructs for Various Human Disease Therapies.Pharmaceutics · 2019Review
- Identification of Cysteine-Rich Angiogenic Inducer 61 as a Potential Antifibrotic and Proangiogenic Mediator in Scleroderma.Arthritis & rheumatology (Hoboken, N.J.) · 2019Article
- Therapeutic vascular growth in the heart.Vascular biology (Bristol, England) · 2019Review
- Therapeutic Benefit and Gene Network Regulation by Combined Gene Transfer of Apelin, FGF2, and SERCA2a into Ischemic Heart.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- The matricellular protein CCN1 controls retinal angiogenesis by targeting VEGF, Src homology 2 domain phosphatase-1 and Notch signaling.Development (Cambridge, England) · 2015Article
- Internal ribosome entry site-based vectors for combined gene therapy.World journal of experimental medicine · 2015Review
- Genome-wide mRNA expression profiling in vastus lateralis of COPD patients with low and normal fat free mass index and healthy controls.Respiratory research · 2015Article
- Repeatability, reproducibility and standardisation of a laser Doppler imaging technique for the evaluation of normal mouse hindlimb perfusion.Sensors (Basel, Switzerland) · 2012Article
- The matricellular protein cysteine-rich protein 61 (CCN1/Cyr61) enhances physiological adaptation of retinal vessels and reduces pathological neovascularization associated with ischemic retinopathy.The Journal of biological chemistry · 2011Article
- Update on gene therapy for myocardial ischaemia and left ventricular systolic dysfunction or heart failure.Archives of cardiovascular diseasesReview
Corrections and comments
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Authors and funding
8 authors.
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Abstract
Due to the lack of an adequate conventional therapy against lower limb ischemia, gene transfer for therapeutic angiogenesis is seen as an attractive alternative. However, the possibility of side effects, due to the expression of large amounts of angiogenic factors, justifies the design of devices that express synergistic molecules in low controlled doses. We have developed an internal ribosome entry site (IRES)-based bicistronic vector expressing two angiogenic molecules, fibroblast growth factor 2 (FGF2), and Cyr61. Through electrotransfer into the ApoE(-/-) mice hindlimb ischemic muscle model, we show that the IRES-based vector gives more stable expression than either monocistronic plasmid. Furthermore, laser Doppler analysis, arteriography, and immunochemistry clearly show that the bicistronic vector promotes a more abundant and functional revascularization than the monocistronic vectors, despite the fact that the bicistronic system produces 5-10 times less of each angiogenic molecule. Furthermore, although the monocistronic Cyr61 vector accelerates B16 melanoma growth in mice, the bicistronic vector is devoid of such side effects. Our results show an active cooperation of FGF2 and Cyr61 in therapeutic angiogenesis of hindlimb ischemia, and validate the use of IRES-based bicistronic vectors for the coexpression of controlled low doses of therapeutic molecules, providing perspectives for a safer gene therapy of lower limb ischemia.
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