Antisense antiviral compound and method for treating arenavirus infection
First Claim
1. A method of inhibiting viral infection in mammalian cells by an Arenavirus in the Arenaviridae family, comprising (a) exposing the cells to an antisense oligonucleotide compound characterized by:
- (i) a substantially uncharged, nuclease-resistant backbone, (ii) capable of uptake by mammalian host cells, (iii) containing between 12-40 nucleotide bases, and (iv) having a targeting sequence of at least 12 subunits complementary to SEQ ID NO;
1 at the 5′
terminus of the vRNA, vcRNA and/or mRNA species of the virus, and (b) by said exposing, forming a heteroduplex structure (i) composed of the virus'"'"' vRNA or vcRNA strand and the oligonucleotide compound, and (ii) characterized by a Tm of dissociation of at least 45°
C.
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Accused Products
Abstract
The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Arenaviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of Arenavirus infection in a mammal. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides have a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with viral RNA sequences within a 19 nucleotide region of the 5′-terminal regions of the viral RNA, viral complementary RNA and/or mRNA identified by SEQ ID NO:1.
19 Citations
17 Claims
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1. A method of inhibiting viral infection in mammalian cells by an Arenavirus in the Arenaviridae family, comprising
(a) exposing the cells to an antisense oligonucleotide compound characterized by: -
(i) a substantially uncharged, nuclease-resistant backbone, (ii) capable of uptake by mammalian host cells, (iii) containing between 12-40 nucleotide bases, and (iv) having a targeting sequence of at least 12 subunits complementary to SEQ ID NO;
1 at the 5′
terminus of the vRNA, vcRNA and/or mRNA species of the virus, and(b) by said exposing, forming a heteroduplex structure (i) composed of the virus'"'"' vRNA or vcRNA strand and the oligonucleotide compound, and (ii) characterized by a Tm of dissociation of at least 45°
C. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 17)
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11. An antisense oligonucleotide compound for use in inhibiting viral infection in mammalian cells by an Arenavirus in the Arenaviridae family, characterized by:
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(i) a substantially uncharged, nuclease-resistant backbone, (ii) capable of uptake by mammalian host cells, (iii) containing between 12-40 nucleotide bases, (iv) having a targeting sequence of at least 12 subunits contained in either SEQ ID NO;
4 or 5; and
(v) capable of binding to the virus'"'"' vRNA/vcRNA or mRNA strands to form a heteroduplex structure having by a Tm of dissociation of at least 45°
C. - View Dependent Claims (12, 13, 14, 15, 16)
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Specification