Evaluation of Baculoviruses as Gene Therapy Vectors for Brain Cancer

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

Viruses

MDPI

Lugar: Basilea; Año: 2023 vol. 15 p. 1 - 22

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.