Intracranial injection of genetically modified, mosquito non-transmissible Zika virus: Safety in primates and ramifications for brain tumor therapy

Alec J. Hirsch; Amanda de Andrade Costa; Cody German; Christopher J. Parkins; Jessica L. Smith; Emilie Russler-Germain; Ashwani Kesarwani; Yuping Li; Verginia Cuzon Carlson; Timothy Carlson; Jodi L. McBride; Sathya Srinivasan; Anne D. Lewis; Xuping Xie; Pei-Yong Shi; Michael S. Diamond; Milan G. Chheda

doi:10.1016/j.xcrm.2025.102509

Intracranial injection of genetically modified, mosquito non-transmissible Zika virus: Safety in primates and ramifications for brain tumor therapy

Alec J. Hirsch
, Amanda de Andrade Costa
, Cody German
, Christopher J. Parkins
, Jessica L. Smith
, Emilie Russler-Germain
, Ashwani Kesarwani
, Yuping Li
, Verginia Cuzon Carlson
, Timothy Carlson
, Jodi L. McBride
, Sathya Srinivasan
, Anne D. Lewis
, Xuping Xie
, Pei-Yong Shi
, Michael S. Diamond
, Milan G. Chheda

Microbiology And Immunology

Research output: Contribution to journal › Article › peer-review

Abstract

Glioblastomas (GBMs) are incurable brain tumors. Zika virus (ZIKV) has specificity in killing GBM stem cells, which drive treatment resistance. In mouse models of GBM, ZIKV also generates an anti-tumor inflammatory response and prolongs survival. To support clinical development and address safety concerns for intra-tumoral treatment, we assessed the effects of injection of an immune-sensitized ZIKV (Δ10 3'-UTR ZIKV), which cannot be transmitted by mosquitos, into non-tumor-bearing rhesus macaque brains. After injection, the primates showed no clinical signs of illness. Histologically, as expected, ZIKV infection elicited mild inflammation, which resolved within 2 weeks. No infectious virus was detected in the brain or any organs at 14 dpi. These findings, along with our preclinical observations, support the development of immune-sensitized ZIKV as a treatment for GBM.

Original language	English (US)
Pages (from-to)	102509
Number of pages	1
Journal	Cell Reports Medicine
Volume	6
Issue number	12
DOIs	https://doi.org/10.1016/j.xcrm.2025.102509
State	Published - Dec 16 2025

Keywords

glioblastoma
oncolytic virus
rhesus macaque
Zika virus

ASJC Scopus subject areas

General Medicine
General Biochemistry, Genetics and Molecular Biology

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10.1016/j.xcrm.2025.102509

Cite this

Hirsch, A. J., de Andrade Costa, A., German, C., Parkins, C. J., Smith, J. L., Russler-Germain, E., Kesarwani, A., Li, Y., Carlson, V. C., Carlson, T., McBride, J. L., Srinivasan, S., Lewis, A. D., Xie, X., Shi, P.-Y., Diamond, M. S., & Chheda, M. G. (2025). Intracranial injection of genetically modified, mosquito non-transmissible Zika virus: Safety in primates and ramifications for brain tumor therapy. Cell Reports Medicine, 6(12), 102509. https://doi.org/10.1016/j.xcrm.2025.102509

Hirsch, AJ, de Andrade Costa, A, German, C, Parkins, CJ, Smith, JL, Russler-Germain, E, Kesarwani, A, Li, Y, Carlson, VC, Carlson, T, McBride, JL, Srinivasan, S, Lewis, AD, Xie, X, Shi, P-Y, Diamond, MS & Chheda, MG 2025, 'Intracranial injection of genetically modified, mosquito non-transmissible Zika virus: Safety in primates and ramifications for brain tumor therapy', Cell Reports Medicine, vol. 6, no. 12, pp. 102509. https://doi.org/10.1016/j.xcrm.2025.102509

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title = "Intracranial injection of genetically modified, mosquito non-transmissible Zika virus: Safety in primates and ramifications for brain tumor therapy",

abstract = "Glioblastomas (GBMs) are incurable brain tumors. Zika virus (ZIKV) has specificity in killing GBM stem cells, which drive treatment resistance. In mouse models of GBM, ZIKV also generates an anti-tumor inflammatory response and prolongs survival. To support clinical development and address safety concerns for intra-tumoral treatment, we assessed the effects of injection of an immune-sensitized ZIKV (Δ10 3'-UTR ZIKV), which cannot be transmitted by mosquitos, into non-tumor-bearing rhesus macaque brains. After injection, the primates showed no clinical signs of illness. Histologically, as expected, ZIKV infection elicited mild inflammation, which resolved within 2 weeks. No infectious virus was detected in the brain or any organs at 14 dpi. These findings, along with our preclinical observations, support the development of immune-sensitized ZIKV as a treatment for GBM.",

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author = "Hirsch, \{Alec J.\} and \{de Andrade Costa\}, Amanda and Cody German and Parkins, \{Christopher J.\} and Smith, \{Jessica L.\} and Emilie Russler-Germain and Ashwani Kesarwani and Yuping Li and Carlson, \{Verginia Cuzon\} and Timothy Carlson and McBride, \{Jodi L.\} and Sathya Srinivasan and Lewis, \{Anne D.\} and Xuping Xie and Pei-Yong Shi and Diamond, \{Michael S.\} and Chheda, \{Milan G.\}",

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AU - Hirsch, Alec J.

AU - de Andrade Costa, Amanda

AU - German, Cody

AU - Parkins, Christopher J.

AU - Smith, Jessica L.

AU - Russler-Germain, Emilie

AU - Kesarwani, Ashwani

AU - Li, Yuping

AU - Carlson, Verginia Cuzon

AU - Carlson, Timothy

AU - McBride, Jodi L.

AU - Srinivasan, Sathya

AU - Lewis, Anne D.

AU - Xie, Xuping

AU - Shi, Pei-Yong

AU - Diamond, Michael S.

AU - Chheda, Milan G.

PY - 2025/12/16

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N2 - Glioblastomas (GBMs) are incurable brain tumors. Zika virus (ZIKV) has specificity in killing GBM stem cells, which drive treatment resistance. In mouse models of GBM, ZIKV also generates an anti-tumor inflammatory response and prolongs survival. To support clinical development and address safety concerns for intra-tumoral treatment, we assessed the effects of injection of an immune-sensitized ZIKV (Δ10 3'-UTR ZIKV), which cannot be transmitted by mosquitos, into non-tumor-bearing rhesus macaque brains. After injection, the primates showed no clinical signs of illness. Histologically, as expected, ZIKV infection elicited mild inflammation, which resolved within 2 weeks. No infectious virus was detected in the brain or any organs at 14 dpi. These findings, along with our preclinical observations, support the development of immune-sensitized ZIKV as a treatment for GBM.

AB - Glioblastomas (GBMs) are incurable brain tumors. Zika virus (ZIKV) has specificity in killing GBM stem cells, which drive treatment resistance. In mouse models of GBM, ZIKV also generates an anti-tumor inflammatory response and prolongs survival. To support clinical development and address safety concerns for intra-tumoral treatment, we assessed the effects of injection of an immune-sensitized ZIKV (Δ10 3'-UTR ZIKV), which cannot be transmitted by mosquitos, into non-tumor-bearing rhesus macaque brains. After injection, the primates showed no clinical signs of illness. Histologically, as expected, ZIKV infection elicited mild inflammation, which resolved within 2 weeks. No infectious virus was detected in the brain or any organs at 14 dpi. These findings, along with our preclinical observations, support the development of immune-sensitized ZIKV as a treatment for GBM.

KW - glioblastoma

KW - oncolytic virus

KW - rhesus macaque

KW - Zika virus

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Intracranial injection of genetically modified, mosquito non-transmissible Zika virus: Safety in primates and ramifications for brain tumor therapy

Abstract

Keywords

ASJC Scopus subject areas

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