Therapeutic polynucleotides, compositions, and methods
This disclosure describes, in one aspect, a composition that generally includes an xNA molecule comprising at least six nucleotides, in an amount effective to improve at least one indicator of myocyte function and a pharmaceutically acceptable carrier. In another aspect, this disclosure describes a method of treating cardiac disease. Generally, the method includes administering to a subject a composition that includes an xNA molecule having at least six nucleotides, in an amount effective to improve at least one indicator of myocyte function, and a pharmaceutically acceptable carrier. In another aspect, this disclosure describes a method for evaluating the efficacy of treatment of cardiac disease. Generally, the method includes administering to a subject a composition that includes a first xNA molecule comprising a predetermined length in an amount effective to increase myocyte relaxation, then selecting a predetermined length of a second xNA molecule for at least one subsequent treatment. If treatment with the first xNA results in more myocyte relaxation than is desired, then the predetermined length of the second xNA molecule is shorter than the predetermined length of the first xNA. If, on the other hand, treatment with the first xNA results in less myocyte relaxation than is desired then the predetermined length of the second xNA molecule is longer than the predetermined length of the first xNA.
1. A method of treating cardiac disease, the method comprising:
administering to a subject a composition comprising:
an xNA molecule comprising at least six nucleotides, in an amount effective to increase the rate of myocyte relaxation, wherein a dissociation constant of the xNA molecule with phospholamban is less than 260 nM; and
a pharmaceutically acceptable carrier.
2. A method comprising:
evaluating the efficacy of treatment of cardiac disease, wherein the treatment comprises administering to a subject a composition comprising a first xNA molecule comprising a predetermined length in an amount effective to increase myocyte relaxation, wherein a dissociation constant of the first xNA molecule with phospholamban is less than 260 nM; and
selecting a predetermined length of a second xNA molecule for at least one subsequent treatment, wherein the change comprises:
the predetermined length of the second xNA molecule is shorter than the predetermined length of the first xNA if treatment with the first xNA results in more myocyte relaxation than is desired; or
the predetermined length of the second xNA molecule is longer than the predetermined length of the first xNA if treatment with the first xNA results in less myocyte relaxation than is desired.
3. The method of claim 1 wherein the xNA molecule comprises a randomized nucleotide sequence.
4. The method of claim 2 wherein the xNA molecule comprises a randomized nucleotide sequence.
5. The method of claim 1 wherein the xNA molecule comprises a mixture of two or more sequences.
6. The method of claim 2 wherein the xNA molecule comprises a mixture of two or more sequences.
7. The method of claim 1 wherein the xNA molecule comprises a mixture of three or more sequences.
8. The method of claim 2 wherein the xNA molecule comprises a mixture of three or more sequences.
9. The method of claim 1 wherein the xNA molecule comprises a pool of randomized nucleotide sequences.
10. The method of claim 2 wherein the xNA molecule comprises a pool of randomized nucleotide sequences.
11. The method of claim 1 wherein the xNA molecule comprises at least ten nucleotides.
12. The method of claim 2 wherein the xNA molecule comprises at least ten nucleotides.
13. The method of claim 1 wherein the dissociation constant of the xNA molecule with phospholamban is less than 20 nM.
14. The method of claim 2 wherein the dissociation constant of the xNA molecule with phospholamban is less than 20 nM.