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Stent-based delivery of adeno-associated viral vectors with sustained vascular transduction and iNOS-mediated inhibition of in-stent restenosis.
Fishbein, I; Guerrero, D T; Alferiev, I S; Foster, J B; Minutolo, N G; Chorny, M; Monteys, A M; Driesbaugh, K H; Nagaswami, C; Levy, R J.
Afiliación
  • Fishbein I; The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Guerrero DT; The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
  • Alferiev IS; The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Foster JB; The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Minutolo NG; The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
  • Chorny M; The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Monteys AM; The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Driesbaugh KH; The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
  • Nagaswami C; The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Levy RJ; The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
Gene Ther ; 24(11): 717-726, 2017 11.
Article en En | MEDLINE | ID: mdl-28832561
In-stent restenosis remains an important clinical problem in the era of drug eluting stents. Development of clinical gene therapy protocols for the prevention and treatment of in-stent restenosis is hampered by the lack of adequate local delivery systems. Herein we describe a novel stent-based gene delivery platform capable of providing local arterial gene transfer with adeno-associated viral (AAV) vectors. This system exploits the natural affinity of protein G (PrG) to bind to the Fc region of mammalian IgG, making PrG a universal adaptor for surface immobilization of vector-capturing antibodies (Ab). Our results: 1) demonstrate the feasibility of reversible immobilization of AAV2 vectors using vector tethering by AAV2-specific Ab appended to the stent surface through covalently attached PrG, 2) show sustained release kinetics of PrG/Ab-immobilized AAV2 vector particles into simulated physiological medium in vitro and site-specific transduction of cultured cells, 3) provide evidence of long-term (12 weeks) arterial expression of luciferase with PrG/Ab-tethered AAV2Luc, and 4) show anti-proliferative activity and anti-restenotic efficacy of stent-immobilized AAV2iNOS in the rat carotid artery model of stent angioplasty.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Reestenosis Coronaria Tipo de estudio: Guideline / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Gene Ther Asunto de la revista: GENETICA MEDICA / TERAPEUTICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Reestenosis Coronaria Tipo de estudio: Guideline / Risk_factors_studies Límite: Animals / Humans / Male Idioma: En Revista: Gene Ther Asunto de la revista: GENETICA MEDICA / TERAPEUTICA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido