SHIP-deficiency to increase megakaryocyte progenitor production
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.
1. A method for improving haematopoietic recovery in a patient in need thereof, comprising:
harvesting megakaryocytes or megakaryocyte progenitors from a patient;
contacting the megakaryocytes or megakaryocyte progenitors with an effective amount of an inhibitor of SH2-containing inositol-5-phosphatase (SHIP) function, thereby expanding the megakaryocytes or megakaryocyte progenitors, wherein the inhibitor of SHIP function is selected from the group consisting of interfering RNA, antisense oligonucleotide, ribozyme, DNAzyme, nucleic acid modifier, PNA, nonstandard nucleic acid, aptamer, decoy, and dominant/negative mutant; and
reinfusing the expanded megakaryocytes or megakaryocyte progenitors into the patient.
2. The method of claim 1 , wherein said method further comprises determining the amount or concentration of megakaryocytes or megakaryocyte progenitors in the patient before said harvesting, after said reinfusing, or both.
3. The method of claim 1 , wherein the inhibitor of SHIP function is an interfering RNA targeted to SHIP mRNA.
4. The method of claim 3 , wherein the interfering RNA is targeted to the SHIP enzymatic domain (inositol 5′-phosphatase domain).
5. The method of claim 3 , wherein the interfering RNA is targeted to the amino-terminal src-homology domain (SH2).
6. The method of claim 1 , wherein the patient is human.
7. The method of claim 1 , wherein the inhibitor of SHIP function is an interfering RNA or antisense oligonucleotide, and wherein the interfering RNA or antisense oligonucleotide is targeted to SHIP mRNA.
8. The method of claim 1 , wherein the inhibitor of SHIP function is an antisense oligonucleotide targeted to SHIP mRNA.
9. The method of claim 3 , wherein the interfering RNA is a small interfering RNA (shRNA).
10. The method of claim 3 , wherein the interfering RNA is a small hairpin RNA (siRNA).
11. The method of claim 7 , wherein the patient is human.
12. The method of claim 6 , wherein the human patient has an anemia.
13. The method of claim 6 , wherein the human patient has undergone a bone marrow transplant.