Inhibition of SHIP to enhance stem cell harvest and transplantation

• US 7,691,821 B2
• Filed: 05/28/2004
• Issued: 04/06/2010
• Est. Priority Date: 09/19/2001
• Status: Expired due to Fees

• Current Assignee: University of South Florida (State University System of Florida)
• Original Assignee: University of South Florida (State University System of Florida)
• Inventors: Wahle, Joseph, Ninos, John, Desponts, Caroline, Kerr, William G.
• Primary Examiner(s): ZARA, JANE J
• Application Number:
  US10/709,801
• Publication Number:
  US 20060223749A1
• Time in Patent Office: 2,139 Days
• Field of Search: 514/44, 435/6, 435/91.1, 435/91.31, 435/455, 435/458, 435/375, 435/372, 536/23.1, 536/24.5
• US Class Current: 514/44.00R
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 2310/111 spanning the whole gene, or a large part of it
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/53 partially self-complementary or closed

Abstract

The instant invention teaches the inhibition of SHIP expression, or function, for the increased efficacy of autologous stem cell transplants. In another embodiment, interference with SHIP function can be used to temporarily expand and mobilize the hematopoietic stem cell compartment to assist with leukapheresis, to promote hematopoietic recovery after myeloablation treatments, to deplete target stem cell clones (such a leukemic clones and other tumor stem cell types), and to deplete, or damage, the repopulating ability of the endogenous hematopoietic stem cell pool in order to allow transplanted hematopoietic stem cells to better home and engraft and to promote in vivo expansion and mobilization of other organ-specific stem cell populations (e.g., mesenchymal, mammary).

Claims

1. A method of increasing the number of hematopoietic stem cells in peripheral blood of a patient, comprising administering an effective amount of an RNA interference molecule targeting SH2-domain containing inositol 5-phosphatase (SHIP) to the patient, wherein the number of hematopoietic stem cells in the peripheral blood of the patient is thereby increased.

2. The method of claim 1, further comprising harvesting the hematopoietic stem cells from the patient after said administering.

3. The method of claim 2, wherein said harvesting comprises leukopheresis.

4. The method of claim 2, further comprising administering the harvested hematopoietic stem cells to the patient.

5. The method of claim 1, wherein the RNA interference molecule is administered intravenously.

6. The method of claim 1, wherein said administering mobilizes the hematopoietic stem cells to the peripheral blood.

7. The method of claim 1, wherein the patient has undergone myeloablation prior to said administering.

8. The method of claim 1, wherein the RNA interference molecule is administered to the patient for 1 week or 2 weeks.

9. The method of claim 1, wherein the subject has cancer or an autoimmune deficiency.

10. The method of claim 4, wherein the subject has cancer or an autoimmune deficiency.