Finderons and methods of their preparation and use
AssigneeHybridon, Inc.
InventorsJohn Goodchild, Thomas E. Leonard
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Abstract
Disclosed is a finderon having the ability to endonucleolytically cleave a sequence of 3' to 5' linked ribonucleotides. The finderon includes a rigid linker comprising at least one non-nucleotidic unit, flanked by first and second flanking regions of at least four contiguous, covalently-linked nucleotides. At least a portion of each flanking region is complementary to a target region on a substrate RNA molecule. Also disclosed are methods of preparing and using a finderon, and kits including a finderon.
Claims15
A method of site-specifically cleaving a single-stranded, RNA-containing substrate, comprising the step of contacting the RNA-containing substrate with a finderon for a time sufficient for the finderon to hybridize to and cleave the RNA containing substrate, the finderon comprising:
- (a) a first flanking region comprising from four to fifteen contiguous, covalently-linked nucleotides, at least a portion of the first flanking region being complementary to a first target region located at a 3' position of a cleavage site on a substrate RNA molecule;
- (b) a second flanking region comprising from four to fifteen contiguous, covalently-linked nucleotides, at least a portion of the second flanking region being complementary to a second target region located at a 5' position of the cleavage site;
- and
- (c) a rigid linker covalently bound to a 3' terminus of the first flanking region and to a 5' terminus of the second flanking region, the linker comprising from one to twelve non-nucleotidic units maintaining the cleavage site in a trigonal bipyramidal transition state conformation, and wherein the non-nucleotidic unit is selected from the group consisting of a cyclohexane diol, asteroid, a lupene diol, an isosorbide, and combinations thereof and a linear distance of about 15 to 30 Angstroms is established between the first and second flanking regions.
Dependencies are inferred from the claim text.