SHIP-deficiency to increase megakaryocyte progenitor production

• US 7,763,592 B1
• Filed: 06/12/2006
• Issued: 07/27/2010
• Est. Priority Date: 11/20/2003
• 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: Desponts, Caroline, Kerr, William G., Perez, Lia Elena
• Primary Examiner(s): Chong; Kimberly
• Application Number:
  US11/451,004
• Time in Patent Office: 1,506 Days
• Field of Search: None
• US Class Current: 514/44.00R
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2217/206 Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/0387 Animal model for diseases of the immune system
• CPC Class Codes: A01K 67/0276 Knock-out vertebrates
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/531 Stem-loop; Hairpin
• CPC Class Codes: C12N 9/16 acting on ester bonds (3.1)

Abstract

The invention concerns a method for increasing megakaryocyte and megakaryocyte progenitor numbers in vitro or in vivo by suppressing SH2-containing inositol-5-phosphatase (SHIP) function in megakaryocytes or megakaryocyte progenitors expressing the SHIP gene. SHIP function can be suppressed by administering an interfering RNA, or other SHIP inhibitor, to the megakaryocytes or megakaryocyte progenitors in vitro or in vivo.

Claims

1. A method for increasing the proliferation of megakaryocyte progenitors in a human having impaired megakaryocyte production, comprising administering an effective amount of an interfering RNA molecule to the human, wherein the interfering RNA molecule is targeted to SH2-containing inositol-5-phosphatase (SHIP) mRNA, and wherein the proliferation of the megakaryocyte progenitors is thereby increased.

2. The method of claim 1, wherein the interfering RNA molecule is targeted to the SHIP enzymatic domain (inositol 5′

-phosphatase domain).

3. The method of claim 1, wherein the interfering RNA molecule is targeted to the amino-terminal src-homology domain (SH2).

4. The method of claim 1, wherein said method further comprises determining whether the proliferation of megakaryocyte progenitors is increased following said administering.

5. The method of claim 1, wherein the method further comprises determining the amount or concentration of megakaryocyte progenitors in the human before said administering, after said administering, or both.

6. The method of claim 1, wherein the interfering RNA molecule is administered to the human locally at the site of the megakaryocyte progenitors.

7. The method of claim 1, wherein the interfering RNA molecule is administered to the human intravenously.

8. The method of claim 7, wherein proliferation of the megakaryocyte progenitors in peripheral blood of the human is thereby increased.

9. The method of claim 1, wherein the human is suffering from an anemia.

10. The method of claim 1, wherein the human has undergone a bone marrow transplant.

11. The method of claim 1, wherein the human has a cell proliferation disorder.

12. The method of claim 1, wherein the human has undergone myeloablative chemotherapy.

13. The method of claim 1, wherein the human has undergone radiation treatment.

14. A method for increasing megakaryocytopoiesis in a human in need thereof, comprising administering an effective amount of an interfering RNA molecule to the human, wherein the interfering RNA molecule is targeted to SH2-containing inositol-5-phosphatase (SHIP) mRNA, and wherein megakaryocytopoiesis is thereby increased.