Splice-region antisense composition and method
AssigneeAVI BioPharma, Inc.
InventorsPatrick L. Iversen, Robert Hudziak
Life of this patent
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Abstract
Antisense compositions targeted against an mRNA sequence coding for a selected protein, at a region having its 5′ end from 1 to about 25 base pairs downstream of a normal splice acceptor junction in the preprocessed mRNA, are disclosed. The antisense compound is RNase-inactive, and is preferably a phosphorodiamidate-linked morpholino oligonucleotide. Such targeting is effective to inhibit natural mRNA splice processing, produce splice variant mRNAs, and inhibit normal expression of the protein.
Claims38
An antisense compound having an uncharged morpholino backbone and a base sequence between 12 and 25 nucleotide bases in length which is complementary to a target region of a selected preprocessed mRNA coding for a protein selected from the group consisting of myc, myb, rel, fos, jun, abl, bcl, p53, an integrin, a cathedrin, a telomerase, a cytokine, a kinase, a receptor protein, hCG, HIV rev, human papilloma virus, and human parvovirus B19,
- where the 5′ end of the target region is 1-25 bases downstream of a normal splice acceptor site in said preprocessed mRNA.
A method of inhibiting normal splicing of mRNA in a eukaryotic cell, comprising
- contacting the cell with an antisense compound having an uncharged morpholino backbone and a base sequence between 12 and 25 nucleotide bases in length which is complementary to a target region of a selected preprocessed mRNA coding for a selected protein;
- where the 5′ end of the target region is 1-25 bases downstream of the a normal splice acceptor site in said preprocessed mRNA,
- wherein the compound:
- is taken up by the cell;
- hybridizes to the target region of preprocessed mRNA in the cell, and
- being so hybridized, prevents splicing at said normal acceptor splice site, such that the splice mechanism proceeds to a downstream splice acceptor sequence in the mRNA, producing a splice variant processed mRNA with a truncated coding sequence.
Dependencies are inferred from the claim text.