Looped, hairpin ribozyme
AssigneeSankyo Company, Limited
InventorsEiko Ohtsuka, Makoto Koizumi
Life of this patent
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Abstract
A polyribonucleotide having a thermodynamically stable loop structure and ribozyme activity and a DNA that codes for the polyribonucleotide. The polyribonucleotide has the following structure ##STR1## Direct administration of the ribozyme polyribonucleotide of the present invention into the body of a patient enables a target polyribonucleotide in the body to be efficiently cleaved, thereby allowing it to be used as an anti-AIDS drug.
Claims22
A polyribonucleotide represented by the following formula (I):
- ##STR22## wherein, U represents an uracil nucleotide, C a cytosine nucleotide, A an adenine nucleotide, and G a guanine nucleotide,
- S represents either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- V represents either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- Q.sub.1 through Q.sub.n may be the same or different from one another and represent either a cytosine nucleotide or guanine nucleotide,
- R.sub.1 through R.sub.n represent nucleotides that are respectively complementary to Q.sub.1 through Q.sub.n,
- W.sub.1 through W.sub.k may be the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- X.sub.1 through X.sub.m may be the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide, and
- k, m and n may be the same or different from one another and represent an integer from 1 to 10.
A polyribonucleotide represented by the following formula (II):
- ##STR23## wherein, U represents an uracil nucleotide, C a cytosine nucleotide, A an adenine nucleotide, and G a guanine nucleotide,
- S represents either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- Q.sub.1 through Q.sub.n may be the same or different from one another and represent either a cytosine nucleotide or guanine nucleotide,
- R.sub.1 through R.sub.n represent nucleotides that are respectively complementary to Q.sub.1 through Q.sub.n,
- W.sub.1 through W.sub.k may be the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- X.sub.1 through X.sub.m may be the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide, and
- k, m and n may be the same or different from one another and represent an integer from 1 to 10.
A process for cleaving a polyribonucleotide .beta.(SEQ ID NO:
- 13) at a site indicated with an arrow in the following formula (III) comprising contacting a substrate polyribonucleotide .beta. in the formula (III) with a ribozyme polyribonucleotide .alpha. (SEQ ID NO:
- 11) in the following formula (III):
- ##STR24## wherein, U represents an uracil nucleotide, C a cytosine nucleotide, A an adenine nucleotide, and G a guanine nucleotide,
- S represents either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- V represents either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- Q.sub.1 through Q.sub.n are the same or different from one another and represent either a cytosine nucleotide or guanine nucleotide.
- R.sub.1 through R.sub.n represent nucleotides that are respectively complementary to Q.sub.1 through Q.sub.n,
- W.sub.1 through W.sub.k are the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- X.sub.1 through X.sub.m are the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or quanine nucleotide,
- P represents either an uracil nucleotide, adenine nucleotide or cytosine nucleotide,
- Y.sub.1 through Y.sub.k represent nucleotides that are respectively complementary to W.sub.1 through W.sub.k,
- Z.sub.1 through Z.sub.m represent nucleotides that are respectively complementary to X.sub.1 through X.sub.m, and
- k, m and n are the same or different from one another and represent an integer from 1 to 10.
A process for cleaving a polyribonucleotide .delta. (SEQ ID NO:
- 13) at a site indicated with an arrow in the following formula (IV) comprising contacting a substrate polyribonucleotide .delta. in the following formula (IV) with a ribozyme polyribonucleotide .gamma. (SEQ ID NO:
- 12) in the following formula (IV):
- ##STR25## wherein, U represents an uracil nucleotide, C a cytosine nucleotide, A an adenine nucleotide, and G a guanine nucleotide,
- S represents either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- Q.sub.1 through Q.sub.n are the same or different from one another and represent either a cytosine nucleotide or guanine nucleotide,
- R.sub.1 through R.sub.n represent nucleotides that are respectively complementary to Q.sub.1 through Q.sub.n,
- W.sub.1 through W.sub.k are the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- X.sub.1 through X.sub.m are the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- P represents either an uracil nucleotide, adenine nucleotide or cytosine nucleotide.
- Y.sub.1 through Y.sub.k represent nucleotide that are respectively complementary to W.sub.1 through W.sub.k,
- Z.sub.1 through Z.sub.m represent nucleotides that are respectively complementary to X.sub.1 through X.sub.m, and
- k, m and n are the same or different from one another and represent an integer from 1 to 10.
A polyribonucleotide containing the nucleotide sequence represented by the following formula (V) (SEQ ID NO:
- 14):
- ##STR26## wherein, U represents an uracil nucleotide, C a cytosine nucleotide, A an adenine nucleotide, and G a guanine nucleotide,
- S represents either an adenine nucleotide or cytosine nucleotide,
- Q.sub.1 through Q.sub.n may be the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- R.sub.1 through R.sub.n represent nucleotides that are respectively complementary to Q.sub.1 through Q.sub.n,
- W.sub.1 through W.sub.4 may be the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- X.sub.1 through X.sub.m may be the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide, and m and n may be the same or different from each other and represent an integer from 1 to 10.
A process for cleaving a polyribonucleotide .zeta. (SEQ ID NO:
- 15), which is included in the nucleotide sequence represented by a formula (VI), at a site indicated with an arrow in the formula (VI) comprising contacting a substrate polyribonucleotide in the following formula (VI) with a ribozyme polyribonucleotide .epsilon. (SEQ ID NO:
- 14), which is included in the nucleotide sequence represented by the following formula (VI):
- ##STR27## wherein, U represents an uracil nucleotide, C a cytosine nucleotide, A an adenine nucleotide, and G a quanine nucleotide,
- S represents either an adenine nucleotide or a cytosine nucleotide,
- Q.sub.1 through Q.sub.n are the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- R.sub.1 through R.sub.n represent nucleotides that are respectively complementary to Q.sub.1 through Q.sub.n,
- W.sub.1 through W.sub.4 are the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- X.sub.1 through X.sub.m are the same or different from one another and represent either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- P represents either an uracil nucleotide, adenine nucleotide, cytosine nucleotide or guanine nucleotide,
- L represents either an uracil nucleotide, adenine nucleotide or cytosine nucleotide,
- V represents either an adenine nucleotide when S is a cytosine nucleotide or an uracil or cytosine nucleotide when S is an adenine nucleotide,
- Y.sub.1 through Y.sub.4 represent nucleotides that are respectively complementary to W.sub.1 through W.sub.4,
- Z.sub.1 through Z.sub.m represent nucleotides that are respectively complementary to X.sub.1 through X.sub.m, and
- m and n are the same or different from each other and represent an integer from 1 to 10.
Dependencies are inferred from the claim text.