 Xylofuranosly-containing nucleoside phosphoramidites and polynucleotides |
| What is claimed is: 1. A compound having the formula I: ##STR5## wherein, R.sub.1 is OH, O--R.sub.3,... |
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| Substituted indazole-O-glucosides |
| OF THE INVENTION All diabetics, regardless of their genetic and environmental backgrounds, have in ... |
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| Production in Escherichia coli of extracellular Serratia spp. hydrolases |
| We claim: 1. A method of producing an extracellular hydrolytic Serratia spp. enzyme selected from ... |
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| Modular assembly of antibody genes, antibodies prepared thereby and use |
| What is claimed is: 1. A polynucleotide molecule encoding an immunoglobulin fragment, said ... |
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| Cytoplasmic bacteriophage display system |
| The present invention relates, in one aspect, to a display vector comprising DNA encoding a portion ... |
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| Diagnosis of alzheimer disease stage by mononuclear cell cytokine secretions |
| AND ADVANTAGES According to the present invention, a method of diagnosing and determining the ... |
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| Polyvalent display libraries |
| I. General The present invention is directed to inter alia two related but self-sufficient ... |
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| Synthetic human neutralizing monoclonal antibodies to human immunodeficiency virus |
| OF THE INVENTION A. Definitions Amino Acid Residue: An amino acid formed upon chemical digestion (... |
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| Pharmaceutical and diagnostic business systems and methods |
| Improved business methods, devices, and systems for utilizing genetic information are provided. A... |
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Auto-ligating oligonucleotide compounds
| Details |
Inventors: Gryaznov, Sergei M.;
Assignee: Lynx Therapeutics, Inc. (Hayward, CA)
Primary Examiner: Fleisher; Mindy
Assistant Examiner: Guzo; David
Attorney, Agent or Firm: Cooley Godward Castro Huddleson & Tatum
The invention provides compositions and a method for delivering an antisense compound or probe to a target polynucleotide. The compositions of the invention comprise a plurality of compounds each having an oligonucleotide moiety from about 4 to 12 monomers in length whose 3' and/or 5' termini have been modified by the addition of one or more terminal binding moieties. Whenever the oligonucleotide moieties specifically anneal to a target polynucleotide in a contiguous end-to-end fashion, the terminal binding moieties are capable of spontaneously interacting with one another to form a covalent linkages or stable complexes so that an effective antisense compound or probe is formed. The invention facilitates the delivery of antisense compounds to their targets and reduces the likelihood of nonspecific binding to non-target structures. |
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DETAILED DESCRIPTION OF THE INVENTION The invention relates to a method and compositions for in situ formation of an effective antisense compound or probe on a target polynucleotide.
Compositions of the invention comprise a plurality of component compounds, preferably from two to five, each of which comprises an oligonucleotide moiety and at least one terminal binding moiety.
The components of the composition assemble spontaneously upon annealing to the target polynucleotide which serves as a template for holding pairs of terminal binding moieties in juxtaposition for ligation or for the formation of non-covalent complexes.
Preferably, oligonucleotide moieties of the compositions are selected so that they undergo either Watson-Crick type base pairing with single stranded polynucleotide targets or Hoogsteen or reverse Hoogsteen types of binding with double stranded target polynucleotides.
In embodiments where triplex formation is desired, there are constraints on the selection of target sequences.
Generally, third strand association via Hoogsteen type of binding is most stable along homopyrimidine-homopurine tracks in a double stranded target.
Usually, base triplets form in T-A*T or C-G*C motifs (where "-" indicates Watson-Crick pairing and "*" indicates Hoogsteen type of binding), however, other motifs are also possible.
For example, Hoogsteen base pairing permits parallel and antiparallel orientations between the third strand (the Hoogsteen strand) and the purine-rich strand of the duplex to which the third strand binds, depending on conditions and the composition of the strands.
There is extensive guidance in the literature for selecting appropriate sequences, orientation, conditions, nucleoside type (e.
g.
whether ribose or deoxyribose nucleosides are employed), base modifications (e.
g.
methylated cytosine, and the like) in order to maximize, or otherwise regulate, triplex stability as desired in particular embodiments, e.
g.
Roberts et al, Proc.
Natl.
Acad.
Sci.
, 88: 9397-9401 (1991); Roberts et al, Science, 258: 1463-1466 (1992); Distefano et al, Proc
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Gene Therapy 
