Most human protein therapeutics require frequent dosing due to rapid clearance of the proteins from the body. Development of second generation protein pharmaceuticals that can be injected less frequently is of considerable interest to patients and healthcare providers. We propose to create long-acting forms of IL-11 and TPO by fusion of these proteins to a naturally occurring protein with a long circulating half-life. These modified proteins will possess biological activities equal or superior to the corresponding natural proteins in vivo, but will require less frequent dosing, on the order of once every one to two weeks, rather than daily or every other day. During Phase I we will construct the IL-11 and TPO fusion proteins and demonstrate that they possess wild type in vitro bioactivities. During Phase II, we will develop manufacturing processes to produce sufficient quantities of the modified proteins for testing in animal disease models. The improved characteristics of the novel proteins will reduce the amount of protein required per patient, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. These proteins will find utility in treating thrombocytopenia resulting from myelosuppressive chemotherapy and drug complications. PROPOSED COMMERCIAL APPLICATIONS: Approximately 25% of cancer patients receiving chemotherapy develop treatment-limiting thrombocytopenia. The long-acting, IL-11 and TPO proteins under development will boost platelet numbers and allow these patients to receive full-dose chemotherapy, potentially improving survival rates. These modified proteins will require much less frequent dosing than existing products, providing significant cost savings to patients and healthcare providers. Additional expected benefits include improved drug efficacy, reduced toxicity and improved patient quality of life.