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Intranasal administration in mice of peptide-conjugated Morpholinos

Peptide-conjugated Morpholinos were administered intranasally to mice to alter the immune response to subsequent intranasal influenza doses. "BALB/c mice were anesthetized with ketamine, followed by i.n. administration with 100 mg (approximately 5 mg/kg) PPMO (in 40 ml of PBS)." Repeat dosing at 24 hours, influenza inoculation at 48 hours.

"TRIM6 expression was silenced in the lungs of mice via peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO). In line with our results from hDCs and cell lines, the designed TRIM6 PPMOs efficiently and specifically downregulated TRIM6 protein levels in MEFs, resulting in a reduction of ISG54 protein expression upon IFN-b treatement."

"Treatment with PPMOs resulted in 50% reduction in TRIM6 mRNA and protein compared to nontargeting PPMO control in the lungs of infected and noninfected mice."

Rajsbaum R, Versteeg GA, Schmid S, Maestre AM, Belicha-Villanueva A, Martínez-Romero C, Patel JR, Morrison J, Pisanelli G, Miorin L, Laurent-Rolle M, Moulton HM, Stein DA, Fernandez-Sesma A, tenOever BR, García-Sastre A. Unanchored K48-Linked Polyubiquitin Synthesized by the E3-Ubiquitin Ligase TRIM6 Stimulates the Interferon-IKKε Kinase-Mediated Antiviral Response. Immunity. 2014;[Epub ahead of print] doi:10.1016/j.immuni.2014.04.018

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