Intranasal gene transfer by chitosan-DNA nanospheres protects BALB/c mice against acute respiratory syncytial virus infection

Mukesh Kumar, Aruna K. Behera, Richard F. Lockey, Jian Zhang, Guraman Bhullar, Cristina Perez de la Cruz, Li Chen Chen, Kam W. Leong, Shau Ku Huang, Shyam S. Mohapatra

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Abstract

Respiratory syncytial virus (RSV) infection is often associated in infancy with life-threatening bronchiolitis, which is also a major risk factor for the development of asthma. At present, no effective prophylaxis is available against RSV infection. Herein, we describe an effective prophylactic intranasal gene transfer strategy utilizing chitosan-DNA nanospheres (IGT), containing a cocktail of plasmid DNAs encoding all RSV antigens, except L. A single administration of IGT (25 μg/mouse) induces expression of the mRNA and proteins of all antigens in the lung and results in a significant reduction of viral titers and viral antigen load after acute RSV infection of these mice. IGT-administered mice show no significant change in airway reactivity to methacholine and no apparent pulmonary inflammation. Furthermore, IGT results in significant induction of RSV-specific IgG antibodies, nasal IgA antibodies, cytotoxic T lymphocytes, and interferon-γ production in the lung and splenocytes compared with controls. Together, these results demonstrate the potential of IGT against acute RSV infection.

Original languageEnglish
Pages (from-to)1415-1425
Number of pages11
JournalHuman Gene Therapy
Volume13
Issue number12
DOIs
Publication statusPublished - Aug 10 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Kumar, M., Behera, A. K., Lockey, R. F., Zhang, J., Bhullar, G., Perez de la Cruz, C., Chen, L. C., Leong, K. W., Huang, S. K., & Mohapatra, S. S. (2002). Intranasal gene transfer by chitosan-DNA nanospheres protects BALB/c mice against acute respiratory syncytial virus infection. Human Gene Therapy, 13(12), 1415-1425. https://doi.org/10.1089/10430340260185058