Antisense antiviral compound and method for treating ssRNA viral infection
First Claim
1. A method of inhibiting replication of an infecting Dengue virus in a mammalian host cell, the method comprising administering to the infected host cell a virus-inhibitory amount of an antisense oligonucleotide analog compound characterized by:
- (i) a nuclease-resistant backbone,(ii) capable of uptake by mammalian host cells,(iii) containing between 15-40 nucleotide bases,(iv) a substantially uncharged backbone, composed of morpholino subunits linked by phosphorodiamidate intersubunit linkages, joining a morpholino nitrogen of one subunit to a 5′
exocyclic carbon of an adjacent subunit, and(v) having a targeting sequence of at least 15 subunits that is complementary to a region within the 5′
-terminal 25 bases of SEQ ID NO;
6, and by said administering, forming within the host cell, a heteroduplex structure (i) composed of the positive sense strand of the virus and the oligonucleotide compound, and (ii) characterized by a Tm of dissociation of at least 45°
C. and disruption of a stem-loop secondary structure.
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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 Flaviviridae, Picomoviridae, Caliciviridae, Togaviridae, Arteriviridae, Coronaviridae, Astroviridae and Hepeviridae families in the treatment of a viral infection. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with stem-loop secondary structure within the 5′-terminal end 40 bases of the positive-sense RNA strand of the virus.
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Citations
13 Claims
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1. A method of inhibiting replication of an infecting Dengue virus in a mammalian host cell, the method comprising administering to the infected host cell a virus-inhibitory amount of an antisense oligonucleotide analog compound characterized by:
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(i) a nuclease-resistant backbone, (ii) capable of uptake by mammalian host cells, (iii) containing between 15-40 nucleotide bases, (iv) a substantially uncharged backbone, composed of morpholino subunits linked by phosphorodiamidate intersubunit linkages, joining a morpholino nitrogen of one subunit to a 5′
exocyclic carbon of an adjacent subunit, and(v) having a targeting sequence of at least 15 subunits that is complementary to a region within the 5′
-terminal 25 bases of SEQ ID NO;
6, and by said administering, forming within the host cell, a heteroduplex structure (i) composed of the positive sense strand of the virus and the oligonucleotide compound, and (ii) characterized by a Tm of dissociation of at least 45°
C. and disruption of a stem-loop secondary structure. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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Specification