Artículo
Evaluation of Baculoviruses as Gene Therapy Vectors for Brain Cancer
Garcia Fallit, Matías
; Pidre, Matias Luis
; Asad, Antonela Sofía
; Peña Agudelo, Jorge Armando
; Vera, Mariana Belén
; Nicola Candia, Alejandro Javier
; Sagripanti, Sofia Betania; Perez Kuper, Melanie; Amorós Morales, Leslie Cinthya
; Marchesini, Abril
; González, Nazareno
; Caruso, Carla Mariana
; Romanowski, Victor
; Seilicovich, Adriana
; Videla Richardson, Guillermo
; Zanetti, Flavia Adriana
; Candolfi, Marianela
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Fecha de publicación:
02/2023
Editorial:
Multidisciplinary Digital Publishing Institute
Revista:
Viruses
e-ISSN:
1999-4915
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
We aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain.
Palabras clave:
ASTROCYTES
,
BACULOVIRUSES
,
BRAIN
,
GENE THERAPY
,
GLIOBLASTOMA
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Identificadores
Colecciones
Articulos (INEU)
Articulos de INSTITUTO DE NEUROCIENCIAS
Articulos de INSTITUTO DE NEUROCIENCIAS
Articulos(IBBM)
Articulos de INST.DE BIOTECNOLOGIA Y BIOLOGIA MOLECULAR
Articulos de INST.DE BIOTECNOLOGIA Y BIOLOGIA MOLECULAR
Articulos(ICT - MILSTEIN)
Articulos de INST.DE CS. Y TECNOLOGIA "DR. CESAR MILSTEIN"
Articulos de INST.DE CS. Y TECNOLOGIA "DR. CESAR MILSTEIN"
Articulos(INBIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Citación
Garcia Fallit, Matías; Pidre, Matias Luis; Asad, Antonela Sofía; Peña Agudelo, Jorge Armando; Vera, Mariana Belén; et al.; Evaluation of Baculoviruses as Gene Therapy Vectors for Brain Cancer; Multidisciplinary Digital Publishing Institute; Viruses; 15; 3; 2-2023; 1-21
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