Technology ID
TAB-1176
TTP as a Regulator of GM-CSF mRNA Deadenylation and Stability
E-Numbers
E-204-1999-0
Lead Inventor
Carballo, Ester (NIEHS)
Co-Inventors
Lai, Wi (NIEHS)
Blackshear, Perry (NIEHS)
Applications
Vaccines
Therapeutics
Research Materials
Diagnostics
Therapeutic Areas
Reproductive Health
Lead IC
NIEHS
ICs
NIEHS
The disclosed invention provides materials and methods to treat granulocytopenia (low white cell count in the blood) which is characterized by a reduced number of granulocytes (relative) or an absence of granulocytes (absolute). This condition is commonly associated with cancer chemotherapy, but is seen less frequently in a number of conditions including the use of propylthiouracil, radiotherapy for marrow ablation for bone marrow transplantation, aplastic anemia, systemic lupus erythematosus, AIDS and a variety of other situations. The invention proposes a method to increase GM-CSF levels in a treated subject, and this increase is achieved by inhibiting the degradation of GM-CSF messenger RNA (mRNA). Tristetraprolin (TTP) is one member of a family of cys-cys-cys-his (CCCH) zinc finger proteins, and it is a factor that binds to and causes the instability of GM-CSF mRNA. Methods are provided for the development of screening assays for molecules that inhibit the binding of TTP and its related proteins to GM-CSF mRNA, or otherwise inhibit the effect of TTP to promote breakdown of the mRNA, leading in turn to increased mRNA stability and enhanced production of GM-CSF. Compounds identified by such screens, and their derivatives, could be useful in treating granulocytopenia from whatever cause.
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