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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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
id I19-R120-10915-152929
record_format dspace
spelling I19-R120-10915-1529292023-05-13T04:07:06Z http://sedici.unlp.edu.ar/handle/10915/152929 issn:1999-4915 Evaluation of baculoviruses as gene therapy vectors for brain cancer 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 2023 2023-05-12T18:30:57Z en Biología Ciencias Médicas Baculoviruses Glioblastoma Astrocytes Gene therapy Brain 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. Instituto de Biotecnología y Biología Molecular Articulo Articulo http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) application/pdf
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Ciencias Médicas
Baculoviruses
Glioblastoma
Astrocytes
Gene therapy
Brain
spellingShingle Biología
Ciencias Médicas
Baculoviruses
Glioblastoma
Astrocytes
Gene therapy
Brain
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
Evaluation of baculoviruses as gene therapy vectors for brain cancer
topic_facet Biología
Ciencias Médicas
Baculoviruses
Glioblastoma
Astrocytes
Gene therapy
Brain
description 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.
format Articulo
Articulo
author 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
author_facet 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
author_sort Garcia Fallit, Matías
title Evaluation of baculoviruses as gene therapy vectors for brain cancer
title_short Evaluation of baculoviruses as gene therapy vectors for brain cancer
title_full Evaluation of baculoviruses as gene therapy vectors for brain cancer
title_fullStr Evaluation of baculoviruses as gene therapy vectors for brain cancer
title_full_unstemmed Evaluation of baculoviruses as gene therapy vectors for brain cancer
title_sort evaluation of baculoviruses as gene therapy vectors for brain cancer
publishDate 2023
url http://sedici.unlp.edu.ar/handle/10915/152929
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