Evaluation of baculoviruses as gene therapy vectors for brain cáncer

GARCÍA FALLIT, MATÍAS; PIDRE, MATÍAS L.; ANTONELA ASAD; PEÑA AGUDELO, JORGE A.; VERA, MB; NICOLA CANDIA, ALEJANDRO J; SAGRIPANTI, SB; PEREZ KUPER, M; AMOROS MORALES, LC; MARCHESINI, A; GONZALEZ, NAZARENO; CARUSO, CARLA; ROMANOWSKI, VÍCTOR; SEILICOVICH, ADRIANA; VIDELA-RICHARDSON, GA; FLAVIA ZANETTI; CANDOLFI, MARIANELA

VIRUSES

MDPI

Año: 2023

We aimed to assess the potential of baculoviral vectors (BV) for brain cancer genetherapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, butfor which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescentreporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïveand glioma-bearing mice were intracranially injected with BVs to assess transduction andneuropathology. 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-mediatedtransduction and showed strong correlation with clathrin expression, a protein that interacts withthe baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normaland neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgeneexpression was stable for at least 21 days in the brain of naïve mice, but it was significantlyreduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVsefficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans donot present pre-existing immunity against BVs, these vectors may constitute a valuable tool for thedelivery of therapeutic genes into the brain.