Evaluation of Baculoviruses as Gene Therapy Vectors for Brain Cancer

PIDRE, MATÍAS L.; VERA, MARIANA B.; PÉREZ KUPER, MELANIE; GONZALEZ, NAZARENO; SEILICOVICH, ADRIANA; CANDOLFI, MARIANELA; ASAD, ANTONELA S.; NICOLA CANDIA, ALEJANDRO J.; AMORÓS MORALES, LESLIE C.; CARUSO, CARLA M.; VIDELA-RICHARDSON, GUILLERMO A.; GARCIA FALLIT, MATÍAS; PEÑA AGUDELO, JORGE A.; SAGRIPANTI, SOFIA B.; MARCHESINI, ABRIL; ROMANOWSKI, VÍCTOR; ZANETTI, FLAVIA A.

Viruses

MDPI

Año: 2023 vol. 15 p. 1 - 22

1999-4915

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.