Oligonucleotide compositions and their use to induce differentiation of cells

Abstract

The present invention provides compositions comprising a 3′-OH, 5′-OH, chemically unmodified, synthetic phosphodiester nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4, and a pharmaceutically acceptable carrier, wherein the compositions are useful to induce differentiation of cells or to stimulate differentiation or production of pluripotent cells. The present invention provides methods of using these compositions to induce differentiation of pluripotent cells, including bone marrow derived cells, and to treat disease associated with insufficient differentiation of cells in animals and humans, including but not limited to leukemia, lymphoma, non-malignant blood disorders such as hemoglobinopathies, sickle cell disease, myelodysplastic syndrome, pancytopenia, anemia, thrombocytopenia and leukopenia.

Description

PRIOR RELATED APPLICATIONS [0001] The present application claims priority to U.S. provisional patent application Ser. No. 60 / 286,158 filed Apr. 24, 2001. This application is a divisional of U.S. patent application Ser. No. 10 / 127,645 filed Apr. 22, 2002, now allowed, the contents of which are incorporated herein by reference.SEQUENCE LISTING [0002] The content of the sequence listing information is identical to the paper sequence listing provided in U.S. patent application Ser. No. 10 / 127,645 filed Apr. 22, 2002, and includes no new matter. FIELD OF THE INVENTION [0003] The present invention provides compositions comprising specific oligonucleotides combined with a pharmaceutically acceptable carrier, wherein the compositions are useful to induce differentiation of cells, including pluripotent cells, leukemic cells, lymphoma cells and bone marrow-derived cells, and to treat diseases such as leukemia, lymphoma and disorders associated with insufficient differentiation of cells. BACKG...

AI Technical Summary

Benefits of technology

[0012] The compositions of the present invention may also be administered to an animal or human together with other therapies as a combination therapy. These therapies may include administration of therapeutic compounds or radiation therapy. The compositions of the present invention may be administered before, after, or concomitantly with the other therapy. Such combination therapy may augment the net therapeutic effect on the animal or human. The compositions of the present invention may be administered alone, or in combination with other therapeutic modalities including, but not limited to, chemotherapeutic agents, differentiating agents, immunotherapeutic agents, antimicrobial agents, antiviral agents or in combination with radiation therapy.

[0036] Still another object of the present invention is to provide a composition that is minimally toxic to the recipient.

Problems solved by technology

Insufficient production of cells destined to become erythrocytes or granulocytes is associated with numerous problems, including but not limited to, reduced delivery of oxygen to cells, decreased immune function, and clotting abnormalities.

Various therapies, including expensive chemotherapies, are often required to stimulate production of red and white cells.

Most prior art differentiating therapies have proven to be less than adequate for clinical applications.

Many of these therapies are inefficient or toxic, have significant adverse effects and are debilitating for the recipient.