Multivalent aptamer complexes
AssigneeWake Forest University Health Sciences
InventorWilliam H. Gmeiner
Life of this patent
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Abstract
A compound of the formula A-B-C, is provided, wherein: A is a first nucleic acid that specifically binds to an extracellular surface protein expressed by a cell of interest, B is an alkyl linker; and C is a second nucleic acid that hybridizes to a complementary nucleic acid. In some embodiments, the first nucleic acid is an aptamer. In some embodiments, the nucleic acid comprises an active compound, particularly cytotoxic nucleotides such as poly-FdUMP. Compositions and methods of using such compounds for treating and/or detecting cancer are also described.
Claims25
A method of introducing a nucleic acid of interest into a cell of interest, comprising contacting a composition to said cell under conditions in which said nucleic acid of interest is internalized into said cell;
- said composition comprising a pair of compounds, at least one member of said pair of compounds comprising said nucleic acid of interest, and each member of said pair having a second nucleic acid that is complementary to and hybridized to the second nucleic acid of the other member of said pair;
- each of said compounds independently having the formula A-B-C, wherein:
- A is a first nucleic acid that specifically binds to an extracellular surface protein expressed by a cell of interest,
- B is an alkyl linker;
- and
- C is said second nucleic acid;
- wherein said first and/or second nucleic acid of at least one of said compounds comprises poly-FdUMP;
- and
- wherein said second nucleic acid of each of said compounds is DNA.
A method of introducing a nucleic acid of interest into a cell of interest, comprising contacting a composition to said cell under conditions in which said nucleic acid of interest is internalized into said cell;
- said composition comprising a pair of compounds, at least one member of said pair of compounds comprising said nucleic acid of interest, and each member of said pair having a second nucleic acid that is complementary to and hybridized to the second nucleic acid of the other member of said pair;
- each of said compounds independently having the formula A-B-C, wherein:
- A is a first nucleic acid that specifically binds to an extracellular surface protein expressed by a cell of interest,
- B is an alkyl linker;
- and
- C is said second nucleic acid;
- wherein said first and/or second nucleic acid of at least one of said compounds comprises poly-FdUMP, and
- wherein each of said compounds further comprises a flexible alkyl linker included within said second nucleic acid.
A method of introducing a nucleic acid of interest into a cell of interest, comprising contacting a composition to said cell under conditions in which said nucleic acid of interest is internalized into said cell;
- said composition comprising a pair of compounds, at least one member of said pair of compounds comprising said nucleic acid of interest, and each member of said pair having a second nucleic acid that is complementary to and hybridized to the second nucleic acid of the other member of said pair;
- each of said compounds independently having the formula A-B-C, wherein:
- A is a first nucleic acid that specifically binds to an extracellular surface protein expressed by a cell of interest,
- B is an alkyl linker;
- and
- C is said second nucleic acid;
- wherein said first and/or second nucleic acid of at least one of said compounds comprises a cytotoxic nucleoside or nucleotide;
- and
- wherein said second nucleic acid of each of said compounds is DNA.
A method of introducing a nucleic acid of interest into a cell of interest, comprising contacting a composition to said cell under conditions in which said nucleic acid of interest is internalized into said cell;
- said composition comprising a pair of compounds, at least one member of said pair of compounds comprising said nucleic acid of interest, and each member of said pair having a second nucleic acid that is complementary to and hybridized to the second nucleic acid of the other member of said pair;
- each of said compounds independently having the formula A-B-C, wherein:
- A is a first nucleic acid that specifically binds to an extracellular surface protein expressed by a cell of interest,
- B is an alkyl linker;
- and
- C is said second nucleic acid;
- and wherein at least one of said first nucleic acids is a DNA having the sequence of SEQ ID NO:
- 1.
Dependencies are inferred from the claim text.