OLIGONUCLEOTIDE COMPOUND AND METHOD FOR TREATING NIDOVIRUS INFECTIONS
First Claim
1. An oligonucleotide compound, which is composed of morpholino subunits and uncharged, phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′
- exocyclic carbon of an adjacent subunit, for use in inhibiting replication of a nidovirus in host cells, characterized by;
(i) a nuclease-resistant backbone,(ii) capable of uptake by virus-infected host cells,(iii) containing between 8-25 nucleotide bases,(iv) having a sequence that is complementary to at least 12 contiguous bases contained in SEQ ID NO;
1; and
(v) capable of forming with SEQ ID NO;
1, a heteroduplex structure characterized by a Tm of dissociation of at least 45°
C.
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Abstract
A method and oligonucleotide compound for inhibiting replication of a nidovirus in virus-infected animal cells are disclosed. The compound (i) has a nuclease-resistant backbone, (ii) is capable of uptake by the infected cells, (iii) contains between 8-25 nucleotide bases, and (iv) has a sequence capable of disrupting base pairing between the transcriptional regulatory sequences in the 5′ leader region of the positive-strand viral genome and negative-strand 3′ subgenomic region. In practicing the method, infected cells are exposed to the compound in an amount effective to inhibit viral replication.
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Citations
14 Claims
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1. An oligonucleotide compound, which is composed of morpholino subunits and uncharged, phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′
- exocyclic carbon of an adjacent subunit, for use in inhibiting replication of a nidovirus in host cells, characterized by;
(i) a nuclease-resistant backbone, (ii) capable of uptake by virus-infected host cells, (iii) containing between 8-25 nucleotide bases, (iv) having a sequence that is complementary to at least 12 contiguous bases contained in SEQ ID NO;
1; and(v) capable of forming with SEQ ID NO;
1, a heteroduplex structure characterized by a Tm of dissociation of at least 45°
C. - View Dependent Claims (2, 3, 4, 5, 6, 7)
- exocyclic carbon of an adjacent subunit, for use in inhibiting replication of a nidovirus in host cells, characterized by;
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8. An oligonucleotide compound, which is composed of morpholino subunits and uncharged, phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′
- exocyclic carbon of an adjacent subunit, for use in inhibiting replication of a nidovirus in host cells, characterized by;
(i) a nuclease-resistant backbone, (ii) capable of uptake by virus-infected host cells, (iii) containing between 8-25 nucleotide bases, (iv) having a sequence that is complementary to at least 12 contiguous bases contained in SEQ ID NO;
3; and(v) capable of forming with SEQ ID NO;
3, a heteroduplex structure characterized by a Tm of dissociation of at least 45°
C. - View Dependent Claims (9, 10, 11, 12, 13, 14)
- exocyclic carbon of an adjacent subunit, for use in inhibiting replication of a nidovirus in host cells, characterized by;
Specification