Patent ID: 7754202

Claim:
A method for rendering a subpopulation of mammalian hematopoietic stem cells susceptible to divalent ligand-induced growth, proliferation or differentiation, which method comprises transducing one or more cells of a population of mammalian primary hematopoietic stem cells with at least one retroviral vector comprising at least one recombinant DNA construct encoding a fusion protein which comprises at least one signaling domain derived from an intracellular portion of a thrombopoietin receptor and at least one ligand-binding domain derived from F36V which is heterologous with respect to the signaling domain and binds to a selected divalent ligand capable of inducing association of two or more molecules of F36V such that upon exposure of the transduced cells to a concentration of the divalent ligand having the formula: effective to induce association of two or more of the encoded fusion proteins, growth, proliferation or differentiation of said cells is induced; wherein X and X′ can be O, NH, or CH 2 ; L is a covalently linker moiety; wherein G and G′ are independently selected from the group comprised of B 1 and B 2 are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, substituted aryl, aryl, or heteroaryl moieties; Y is O, S, NH, —NH(C═O)—, NH(C═O)—O—, NH(SO 2 )—, NR 3 , or a covalent bond; R 1 , R 1′ , and R 2 are the same or different and are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, hetero alkyl, heteroalkenyl, heteroalkynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkayl, substituted aryl, aryl, or heteroaryl moieties; n and n′ are each independently 1 or 2; wherein at least one of X—R 1 and X′—R 1′ is independently a moiety: wherein R 4 is hydrogen; branched, unbranched, cyclic, saturated or unsaturated, substituted or unsubstituted aliphatic; branched, unbranched or cyclic heteroaliphatic; aryl or heteroaryl; R 5 is a branched, unbranched or cyclic, aliphatic moiety of 1 to 8 carbon atoms; R 6 is a substituted or unsubstituted aliphatic, heteroaliphatic, heterocyclic, aryl or heteroaryl moiety; R 7 is hydrogen or a reactive functional group permitting covalent attachment to a linker moiety; and wherein the transduction is carried out in vivo or ex vivo and wherein said transduced cells are suitable for introduction into a mammal.