OLIGONUCLEOTIDE SYSTEMS FOR TARGETED INTRACELLULAR DELIVERY
First Claim
1. A method for deriving an oligonucleotide for specific internal delivery to target cells, the method comprising:
- providing a plurality of oligonucleotides; and
selecting at least once with target cells to provide a plurality of internalizing oligonucleotides,wherein at least one oligonucleotide is derived that specifically internalizes into target cells.
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Abstract
The present invention provides methods for deriving oligonucleotides for specific internal delivery to one or more target cell types (e.g., cancer cells). The method generally includes selecting at least once with a target cell type to provide a plurality of internalizing oligonucleotides for the target cell type, and in some embodiments, counter-selecting at least once with a non-target cell type to provide a plurality of oligonucleotides that do not bind to features present in the non-target cell type. Therapeutic and diagnostic compositions including the oligonucleotides, and methods of treatment are also provided.
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Citations
28 Claims
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1. A method for deriving an oligonucleotide for specific internal delivery to target cells, the method comprising:
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providing a plurality of oligonucleotides; and selecting at least once with target cells to provide a plurality of internalizing oligonucleotides, wherein at least one oligonucleotide is derived that specifically internalizes into target cells. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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- 13. An isolated oligonucleotide that specifically internalizes into at least one target cell type.
- 14. An isolated plurality of oligonucleotides that specifically internalizes into at least one target cell type.
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28. A method for determining nucleic sequence motifs associated with internalization of oligonucleotides into target cell type comprising:
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providing a plurality of oligonucleotides; counter-selecting at least once with a non-target cell type to provide a plurality of oligonucleotides that do not bind to features present in the non-target cell type; selecting at least once with a target cell type to provide a plurality of internalizing oligonucleotides for the target cell type; determining at least a portion of the nucleic acid sequence of the plurality of internalizing oligonucleotides for the target cell type; and comparing the nucleic acid sequences, thereby determining common nucleic sequence motifs associated with internalization of oligonucleotides into a first cell type but not a second cell type.
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Specification