Evaluation of baculoviruses as gene therapy vectors for brain cancer

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 evaluate...

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Detalles Bibliográficos
Autores principales: Garcia Fallit, Matías, Pidre, Matías Luis, Asad, Antonela S., Peña Agudelo, Jorge A., Vera, Mariana B., Nicola Candia, Alejandro J., Sagripanti, Sofia B., Pérez Kuper, Melanie, Amorós Morales, Leslie Cinthya, Marchesini, Abril, Gonzalez, Nazareno, Caruso, Carla M., Romanowski, Víctor, Seilicovich, Adriana, Videla Richardson, Guillermo A., Zanetti, Flavia A., Candolfi, Marianela
Formato: Articulo
Lenguaje:Inglés
Publicado: 2023
Materias:
Biología
Ciencias Médicas
Baculoviruses
Glioblastoma
Astrocytes
Gene therapy
Brain
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/152929
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
Descripción
Sumario: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.

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