Oligonucleotide compound and method for treating nidovirus infections
First Claim
1. An antisense compound, which is composed of morpholino subunits and phosphorus-containing intersubunit linkages, which join a morpholino nitrogen of one subunit to a 5′
- exocyclic carbon of an adjacent subunit, for use in inhibiting replication of a nidovirus in mammalian host cells, comprising;
(i) a nuclease-resistant backbone,(ii) 12-25 nucleotide bases, and(iii) a targeting sequence that is complementary to at least 12 contiguous bases contained in SEQ ID NO;
3;
wherein the targeting sequence forms a heteroduplex structure composed of SEQ ID NO;
3 and the antisense compound, SEQ ID NO;
3 comprising a transcriptional regulatory sequence in a 5′
leader region of a positive-strand viral genome, the heteroduplex structure characterized by a Tm, of dissociation of at least 45°
C., wherein the heteroduplex structure disrupts base pairing between the transcriptional regulatory sequence in the 5′
leader region of the positive-strand viral genome and a negative-strand 3′
subgenomic region, thereby inhibiting viral replication.
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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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8 Claims
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1. An antisense compound, which is composed of morpholino subunits and phosphorus-containing intersubunit linkages, which join a morpholino nitrogen of one subunit to a 5′
- exocyclic carbon of an adjacent subunit, for use in inhibiting replication of a nidovirus in mammalian host cells, comprising;
(i) a nuclease-resistant backbone, (ii) 12-25 nucleotide bases, and (iii) a targeting sequence that is complementary to at least 12 contiguous bases contained in SEQ ID NO;
3;wherein the targeting sequence forms a heteroduplex structure composed of SEQ ID NO;
3 and the antisense compound, SEQ ID NO;
3 comprising a transcriptional regulatory sequence in a 5′
leader region of a positive-strand viral genome, the heteroduplex structure characterized by a Tm, of dissociation of at least 45°
C., wherein the heteroduplex structure disrupts base pairing between the transcriptional regulatory sequence in the 5′
leader region of the positive-strand viral genome and a negative-strand 3′
subgenomic region, thereby inhibiting viral replication. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
- exocyclic carbon of an adjacent subunit, for use in inhibiting replication of a nidovirus in mammalian host cells, comprising;
Specification