Viruses (Feb 2023)

Evaluation of Baculoviruses as Gene Therapy Vectors for Brain Cancer

  • Matías Garcia Fallit,
  • Matías L. Pidre,
  • Antonela S. Asad,
  • Jorge A. Peña Agudelo,
  • Mariana B. Vera,
  • Alejandro J. Nicola Candia,
  • Sofia B. Sagripanti,
  • Melanie Pérez Kuper,
  • Leslie C. Amorós Morales,
  • Abril Marchesini,
  • Nazareno Gonzalez,
  • Carla M. Caruso,
  • Víctor Romanowski,
  • Adriana Seilicovich,
  • Guillermo A. Videla-Richardson,
  • Flavia A. Zanetti,
  • Marianela Candolfi

DOI
https://doi.org/10.3390/v15030608
Journal volume & issue
Vol. 15, no. 3
p. 608

Abstract

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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.

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