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- Title
Evaluation of Baculoviruses as Gene Therapy Vectors for Brain Cancer.
- Authors
Garcia Fallit, Matías; Pidre, Matías L.; Asad, Antonela S.; Peña Agudelo, Jorge A.; Vera, Mariana B.; Nicola Candia, Alejandro J.; Sagripanti, Sofia B.; Pérez Kuper, Melanie; Amorós Morales, Leslie C.; Marchesini, Abril; Gonzalez, Nazareno; Caruso, Carla M.; Romanowski, Víctor; Seilicovich, Adriana; Videla-Richardson, Guillermo A.; Zanetti, Flavia A.; Candolfi, Marianela
- Abstract
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.
- Subjects
GENE therapy; BRAIN cancer; BACULOVIRUSES; FLUORESCENT proteins; TRANSGENE expression; COATED vesicles; CANCER genes
- Publication
Viruses (1999-4915), 2023, Vol 15, Issue 3, p608
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v15030608