Antisense antiviral compounds and methods for treating a filovirus infection
First Claim
1. A method of treating Marburg virus infection in a subject, the method comprising:
- administering to a subject a therapeutically effective amount of an antisense oligomer of 12-40 morpholino subunits linked by phosphorous-containing intersubunit linkages which join a morpholino nitrogen of one subunit to a 5′
exocyclic carbon of an adjacent subunit, wherein at least 2 and no more than half of the total number of intersubunit linkages are positively charged at physiological pH; and
comprisinga targeting sequence which forms a heteroduplex with a target sequence of the AUG start-site region of a positive-strand mRNA for Marburg viral protein NP;
wherein the antisense oligomer inhibits virus production.
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Abstract
The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Filoviridae family, and in the treatment of a viral infection. The compounds and methods relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds are morpholino oligonucleotides having: a) a nuclease resistant backbone, b) 15-40 nucleotide bases, and c) a targeting sequence of at least 15 bases in length that hybridizes to a target region selected from the following: i) the Ebola virus AUG start site region of VP24; ii) the Ebola virus AUG start site region of VP35; iii) the Marburg virus AUG start site region of VP24; or iv) the Marburg virus AUG start site region of NP.
91 Citations
13 Claims
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1. A method of treating Marburg virus infection in a subject, the method comprising:
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administering to a subject a therapeutically effective amount of an antisense oligomer of 12-40 morpholino subunits linked by phosphorous-containing intersubunit linkages which join a morpholino nitrogen of one subunit to a 5′
exocyclic carbon of an adjacent subunit, wherein at least 2 and no more than half of the total number of intersubunit linkages are positively charged at physiological pH; and
comprisinga targeting sequence which forms a heteroduplex with a target sequence of the AUG start-site region of a positive-strand mRNA for Marburg viral protein NP; wherein the antisense oligomer inhibits virus production. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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Specification