Compositions and methods using CpG oligonucleotides
Compositions and pharmaceutical compositions are provided herein which can comprise oligonucleotides, such as synthetic CpG oligonucleotides, related to immune responses, and/or other ingredient(s). Compositions and pharmaceutical compositions described herein include those that result in a TLR9 activation. Also described are methods, among other things, for accelerating wound healing, for cell expansion, and improved methods of activated cell expansion by compositions and pharmaceutical compositions herein.
1. A composition comprising:
(i) a synthetic CpG oligonucleotide having the following sequence:
A*T*C*T*C*G*T*A*G*C*A*T*C*T*C*G*T*A*G*C (SEQ ID NO: 17);
A*T*C*T*C*G*G*A*G*C*A*T*C*T*C*G*G*A*G*C (SEQ ID NO: 19);
A*T*G*C*G*T*C*G*G*C*G*A*C*G*T*C*G*T*G*C (SEQ ID NO: 21);
T*A*G*C*G*T*C*G*A*C*G*A*C*G*T*C*G*A*T*G (SEQ ID NO: 22);
A*T*A*T*A*C*T*C*T*A*T*A*G*A*T*T*T*C*T*C (SEQ ID NO: 24),
A*T*C*T*CG*T*A*G*C*A*T*C*T*C*G*T*A*G*C (SEQ ID NO: 25);
A*T*C*T*CG*G*A*G*C*A*T*C*T*C*G*G*A*G*C (SEQ ID NO: 27);
A*T*G*C{circumflex over ( )}G*T*C*G*G*C*G*A*C*G*T*C*G*T*G*C (SEQ ID NO: 29); or
T*A*G*C/G*T*C*G*A*C*G*A*C*G*T*C*G*A*T*G (SEQ ID NO: 30), wherein * indicates a phosphorothioate group and {circumflex over ( )} indicates a phosphodiester group between a C and a G; and
(ii) an excipient, diluent, carrier, or any combination of these.
2. The composition of claim 1 , wherein the synthetic CpG oligonucleotide in the composition is a TLR agonist.
3. The composition of claim 1 , wherein the composition when contacted with a Ramos-Blue B lymphocyte cell, results in an increased concentration of secreted embryonic alkaline phosphatase (SEAP) from the Ramos-Blue B lymphocyte cell compared to an otherwise comparable Ramose-Blue B lymphocyte cell that is not contacted with the composition, in an in vitro assay.
4. The composition of claim 1 , wherein the synthetic CpG oligonucleotide does not contain an epigenetic modification.
5. The composition of claim 1 , wherein the synthetic CpG oligonucleotide comprises a chemical modification to a sugar of a nucleobase.
6. The composition of claim 1 , wherein the composition is a pharmaceutical composition.
7. The composition of claim 6 , wherein the pharmaceutical composition is in unit dose form.
8. The composition of claim 1 , wherein the composition is formulated for topical administration.
9. The composition of claim 8 , wherein the composition formulated for topical administration is in the form of a spray, a cream, a lotion, a powder, a gel, or is comprised on or in a pad, a bandage, or a dressing.
10. The composition of claim 1 , wherein the synthetic CpG oligonucleotide is comprised in a vesicle, a liposome, a micelle, or a particle.
11. A method of accelerating a healing of a wound in a subject in need thereof, the method comprising contacting the wound of the subject with the composition of claim 1 to the subject in need thereof, in an amount effective to accelerate the healing of the wound in the subject, thereby accelerating the healing of the wound as compared to an otherwise comparable wound not contacted with the composition.
12. The method of claim 11 , wherein the subject or the subject in need thereof is a human.
13. The method of claim 11 , wherein the wound is a surgical wound, a scar, an unclean wound, a clean wound, a deep incisional wound, a superficial incisional wound, an ulcer, a diabetic ulcer, a diabetic foot ulcer, a radiation dermatitis, a burn, acne, a cancer, a skin cancer, a psoriasis, a combat wound, an infection, a viral infection, a bacterial infection, a fungal infection, a parasitic infection, a cutaneous infection, a subcutaneous infection, or any combination of these.
14. The method of claim 11 , wherein the contacting comprises contacting a tissue in the subject in need thereof with the composition.
15. The method of claim 14 , wherein the contacting is once, twice, three, four, five, six, seven, eight, nine, or ten times in a 24-hour period.
16. The method of claim 14 , wherein the contacting occurs daily, every other day, every third day, every fourth day, every fifth day, every sixth day, weekly, every two weeks, every three weeks, once a month, once every three months, once every six months, once a year, or as needed.
17. The method of claim 11 , wherein the synthetic CpG oligonucleotide is independently present in the composition in an amount ranging from about 1 ng to about 100 ng, about 100 ng to about 500 ng, about 500 ng to about 1 mg, or about 1 mg to about 100 mg, or about 1 ng to about 25,000 mg.
18. A composition formulated for topical administration comprising:
(i) a CpG oligonucleotide selected from the group consisting of:
A*T*C*T*C*G*T*A*G*C*A*T*C*T*C*G*T*A*G*C (SEQ ID NO: 17),
A*T*G*C*G*T*C*G*G*C*G*A*C*G*T*C*G*T*G*C (SEQ ID NO: 21),
A*T*C*T*C{circumflex over ( )}G*T*A*G*C*A*T*C*T*C*G*T*A*G*C (SEQ ID NO: 25), and
A*T*G*CAG*T*C*G*G*C*G*A*C*G*T*C*G*T*G*C (SEQ ID NO: 29), wherein * indicates a phosphorothioate group and {circumflex over ( )} indicates a phosphodiester group between a C and a G; and
(ii) an excipient,
in an effective amount to treat a wound in a subject in need thereof.
19. The composition of claim 18 , wherein the CpG oligonucleotide is
(SEQ ID NO: 17)
A*T*C*T*C*G*T*A*G*C*A*T*C*T*C*G*T*A*G*C.
20. The composition of claim 18 , wherein the CpG oligonucleotide is
(SEQ ID NO: 25)
A*T*C*T*C ∧ G*T*A*G*C*A*T*C*T*C*G*T*A*G*C.