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2003 | 50 | 3 |

Tytuł artykułu

Construction of a bicistronic proangiogenic expression vector and its application in experimental angiogenesis in vivo

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Manipulation of angiogenesis in vivo is an example of successful gene therapy strate­gies. Overexpression of angiogenic genes like VEGF, FGF or PDGF causes new vessel formation and improves the clinical state of patients. Gene therapy is a very promis­ing procedure but requires large amounts of pharmaceutical-grade plasmid DNA. In this regard we have constructed a bicistronic plasmid DNA vector encoding two proangiogenic factors, VEGF165 and FGF-2. The construct (pVIF) contains the inter­nal ribosome entry site (IRES) of the encephalomyocarditis virus (ECMV) which per­mits both genes to be translated from a single bicistronic mRNA. The IRES sequence allows for a high efficiency of gene expression in vivo. The pVIF vector was character­ized in vitro and in vivo. In vivo angiogenesis studies showed that the bicistronic vec­tor encoding two proangiogenic factors induces the formation of new vessels signifi­cantly more than pVEGF165 or pFGF-2 alone. In our opinion the combined pro- angiogenic approach with VEGF165 and FGF-2 is more powerful and efficient than single gene therapy. We also postulate that IRES sequence can serve as a useful device improving efficiency of gene therapy.

Wydawca

-

Rocznik

Tom

50

Numer

3

Opis fizyczny

p.875-882,fig.

Twórcy

autor
  • Cancer Center, W.Roentgena 5, 02-781 Warsaw, Poland
autor

Bibliografia

  • Attal J, Theron MC, Houdebine LM. (1999) The optimal use of IRES (internal ribosome entry site) in expression vectors. Genet Anal. ; 15: 161-5.
  • Battegay EJ. (1995) Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects. J Mol Med.; 73: 333-46.
  • de Felipe P. (2002) Polycistronic viral vectors. Curr Gene Ther.; 2: 355-78.
  • Dulak J, Jozkowicz A, Guevara I, Dembinska- Kiec A. (1999) Gene transfer of vascular endothelial growth factor and endothelial nitric oxide syntase — implications for gene therapy in cardiovascular diseases. Pol J Pharmacol. ; 51: 233-7.
  • Garcia-Martinez C, Opolon P, Trochon V, Chianale C, Musset K, Lu H, Abitbol M, Perricaudet M, Ragot T. (1999) Angiogenesis induced in muscle by a recombinant adenovirus expressing functional isoforms of basic fibroblast growth factor. Gene Ther.; 6: 1210-21.
  • Gurtu V, Yan G, Zhang G. (1996) IRES bicistronic expression vectors for efficient creation of stable mammalian cell lines. Biochem Biophys Res Commun.; 229: 295-8.
  • Harjai KJ, Chowdhury P, Grines CL. (2002) Therapeutic angiogenesis: a fantastic new adventure. JInterv Cardiol.; 15: 223-30.
  • Hayes AJ. (1999) Antivascular therapy: a new approach to cancer treatment. BMJ.; 318: 853-6.
  • Ibukiyama C. (1996) Angiogenesis. Angiogenic therapy using fibroblast growth factor and vascular endothelial growth factor for ischemic vascular lesions. Jap Heart J.; 37: 285-300.
  • Isner JM, Asahara T. (1998) Therapeutic angiogenesis. FrontBiosc.; 3: 49-69.
  • Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Ashara T, Rosenfield K, Razvi S, Walsh K, Symes JF. (1996a) Clinical evidence of angiogenesis after arterial gene transfer of phVEGF^ in patient with ischaemic limb. Lancet.; 348: 370-4.
  • Isner JM, Walsh K, Symes J, Pieczek A, Takeshita S, Lowry J, Rosenfield K, Weir L, Brogi E, Jurayj D. (1996b) Arterial gene transfer for therapeutic angiogenesis in patients with peripheral artery disease. Hum Gene Ther.; 7: 959-88.
  • Kapturczak M, Zolotukin S, Cross J, Pileggi A, Molano RD, Jorgensen M, Byrne B, Flotte TR, Ellis T, Inveradi L, Ricordi C, Nick H, Atkinson M, Agarwal A. (2002) Transduction of human and mouse pancreatic islet cells using a bicistronic recombinant adeno-associated viral vector. Mol Ther.; 5: 154-60.
  • Kolsut P, Malecki M, Teresinska A, Religa Z, Janik P. (2003) Gene therapy of coronary artery disease. Ann Diagnost Paediatr Pathol.; 7: 19-23.
  • Malecki M, Janik P. (1999) Naczyniowo-srodblonkowy czynnik wzrostu (VEGF) i jego potencjalne aplikacje terapeutyczne w zmianach naczyniowych i nowotworach. Pol Przeg Chir.; 71: 1291-7 (in Polish).
  • Malecki M, Janik P. (2002) Terapia genowa — proby zastosowan klinicznych. Terapia angiogenna. Ordynator Lekow.; 5: 8-12 (in Polish).

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

bwmeta1.element.agro-article-ee316e10-7bbf-415b-8804-6eb04d418024
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