Antisense antiviral compound and method for treating picornavirus infection
First Claim
1. A method of inhibiting viral infection in mammalian cells by an Enterovirus or Rhinovirus in the Picornaviridae 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;
4 in the positive-sense strand of the virus, and (b) by said exposing, forming a heteroduplex structure (i) composed of the virus'"'"' positive sense strand and the oligonucleotide compound, and (ii) characterized by a Tm of dissociation of at least 45°
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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 Picornaviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of Enterovirus and/or Rhinovirus infection in a mammal. The antisense antiviral compounds are substantially uncharged, including partially positively charged, 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 32 nucleotide region of the viral 5′ untranslated region identified by SEQ ID NO:4.
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Citations
21 Claims
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1. A method of inhibiting viral infection in mammalian cells by an Enterovirus or Rhinovirus in the Picornaviridae 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;
4 in the positive-sense strand of the virus, and(b) by said exposing, forming a heteroduplex structure (i) composed of the virus'"'"' positive sense 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, 11, 12, 21)
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13. An antisense oligonucleotide compound for use in inhibiting viral infection in mammalian cells by an Enterovirus or Rhinovirus in the Picornaviridae 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 SEQ ID NO;
6; and
(v) capable of binding to the virus'"'"' positive sense strand to form a heteroduplex structure having by a Tm of dissociation of at least 45°
C. - View Dependent Claims (14, 15, 16, 17, 18, 19, 20)
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Specification