Antisense antiviral agent and method for treating ssRNA viral infection
AssigneeAVI BioPharma, Inc.
InventorsDavid A. Stein, Douglas E. Skilling, Patrick L. Iversen, Alvin W. Smith
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Abstract
The invention provides antisense antiviral compounds and methods of their use in inhibition of growth of viruses of the picornavirus, calicivirus, togavirus and flavivirus families, as in treatment of a viral infection. The antisense antiviral compounds are substantially uncharged oligomers having a targeting base sequence that is substantially complementary to a viral target sequence which spans the AUG start site of the first open reading frame of the viral genome.
Claims37
An antiviral compound directed against an RNA virus from the picornavirus, calicivirus, togavirus or flavivirus families, said virus having a single-stranded, positive sense genome of less than 12 kb and a first open reading frame that encodes a polyprotein containing multiple functional proteins, said compound comprising
- a morpholino oligomer having (a) a sequence of 12 to 40 morpholino subunits, supporting a targeting base sequence that is substantially complementary to a viral target sequence which spans the translation initiation region of said first open reading frame, and (b) a substantially uncharged backbone.
A method of inhibiting replication of an RNA virus from the picomavirus, calicivirus, togavirus or flavivirus families which has a single-stranded, positive sense genome of less than 12 kb, and a first open reading frame that encodes a polyprotein containing multiple functional proteins, comprising
- exposing said virus to a morpholino oligomer having (a) a sequence of 12 to 40 morpholino subunits, supporting a targeting base sequence that is substantially complementary to a viral target sequence which spans the translation initiation region of said first open reading frame, and (b) a substantially uncharged backbone.
A method of confirming the presence of an effective interaction between a picornavirus, calicivirus, togavirus or flavivirus infecting a mammalian subject, and an antisense oligomer targeted against the infecting virus, comprising
- (a) administering said oligomer to the subject, wherein said oligomer has a sequence of 12 to 40 morpholino subunits, supporting a targeting base sequence that is substantially complementary to a viral target sequence which spans the translation initiation region of the first open reading frame of the infecting virus,
- (b) at a selected time after said administering, obtaining a sample of a body fluid from the subject;
- and
- (c) assaying the sample for the presence of a nuclease-resistant heteroduplex comprising the antisense oligomer and a complementary portion of said viral target sequence.
A method of determining the family or genus of an infecting picomavirus, calicivirus, togavirus or flavivirus, the method comprising
- (a) providing a plurality of antisense oligomers, each said oligomer having a base sequence that is substantially complementary to a viral target sequence of a plurality of known viruses selected from picomaviruses, caliciviruses, togaviruses or flaviviruses, wherein each said viral target sequence is (i) common to a virus family or genus, and (ii) not found in humans;
- (b) administering at least one oligomer of the plurality to the subject,
- (c) at a selected time after said administering, obtaining a sample of a body fluid from the subject;
- (d) assaying the sample for the presence of a nuclease-resistant heteroduplex comprising the antisense oligomer and a complementary portion of the viral target sequence, and
- (e) identifying the family or genus of the infecting virus, based on the presence or absence of a heteroduplex comprising an administered antisense oligomer and a complementary portion of said viral target base sequence.
Dependencies are inferred from the claim text.