Inhibition of respiratory syncytial virus infections with morpholino oligomers in cell cultures and in mice

Shen Hao Lai, David A. Stein, Antonieta Guerrero-Plata, Sui Ling Liao, Teodora Ivanciuc, Chao Hong, Patrick L. Iversen, Antonella Casola, Roberto Garofalo

Research output: Contribution to journalArticle

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Abstract

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infants, young children, and high-risk adults. Currently, there is no vaccine to prevent RSV infection, and the available therapeutic agents are of limited utility. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) are a class of antisense agents that can enter cells readily and interfere with viral protein expression through steric blocking of complementary RNA. Two antisense PPMOs, designed to target sequence that includes the 5′-terminal region and translation start-site region of RSV L mRNA, were tested for anti-RSV activity in cultures of two human-airway cell lines. Both PPMOs showed minimal cytotoxicity and one of them, (AUG-2), reduced viral titers by >2.0 log10. Intranasal (i.n.) treatment of BALB/ c mice with AUG-2 PPMO before the RSV inoculation produced a reduction in viral titer of 1.2 log10 in lung tissue at day 5 postinfection (p.i.), and attenuated pulmonary inflammation at day 7 postinfection. These data show that the AUG-2 PPMO possesses potent anti-RSV activity and is worthy of further investigation as a candidate for potential therapeutic application.

Original languageEnglish (US)
Pages (from-to)1120-1128
Number of pages9
JournalMolecular Therapy
Volume16
Issue number6
DOIs
StatePublished - Jun 2008

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Respiratory Syncytial Virus Infections
Morpholinos
Respiratory Syncytial Viruses
Cell Culture Techniques
Complementary RNA
Viral Proteins
Respiratory Tract Infections
Pneumonia
Therapeutics
Vaccines
Cell Line
Lung
Messenger RNA
Peptides

ASJC Scopus subject areas

  • Molecular Biology

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Inhibition of respiratory syncytial virus infections with morpholino oligomers in cell cultures and in mice. / Lai, Shen Hao; Stein, David A.; Guerrero-Plata, Antonieta; Liao, Sui Ling; Ivanciuc, Teodora; Hong, Chao; Iversen, Patrick L.; Casola, Antonella; Garofalo, Roberto.

In: Molecular Therapy, Vol. 16, No. 6, 06.2008, p. 1120-1128.

Research output: Contribution to journalArticle

Lai, SH, Stein, DA, Guerrero-Plata, A, Liao, SL, Ivanciuc, T, Hong, C, Iversen, PL, Casola, A & Garofalo, R 2008, 'Inhibition of respiratory syncytial virus infections with morpholino oligomers in cell cultures and in mice', Molecular Therapy, vol. 16, no. 6, pp. 1120-1128. https://doi.org/10.1038/mt.2008.81
Lai, Shen Hao ; Stein, David A. ; Guerrero-Plata, Antonieta ; Liao, Sui Ling ; Ivanciuc, Teodora ; Hong, Chao ; Iversen, Patrick L. ; Casola, Antonella ; Garofalo, Roberto. / Inhibition of respiratory syncytial virus infections with morpholino oligomers in cell cultures and in mice. In: Molecular Therapy. 2008 ; Vol. 16, No. 6. pp. 1120-1128.
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