Efficient gene delivery to quiescent interleukin-2 (IL-2)-dependent cells by murine leukemia virus-derived vectors harboring IL-2 chimeric envelopes glycoproteins

Interleukin-2 (IL-2) is a cytokine that induces the proliferation of certai n IL-2 receptor expressing quiescent cells, Human IL-2 was fused to the ami no-terminus of amphotropic murine leukemia virus (MLV) envelope glycoprotei ns. Retroviral vectors were pseudotyped with both the IL-2 chimeric envelop e and the wild-type amphotropic MLV envelope. The chimeric IL-2 glycoprotei ns were incorporated on retroviral vectors and the IL-2-displaying vector p articles could bind specifically to cell surface IL-2 receptors. In additio n, the IL-2-displaying vectors could infect proliferating cells through amp hotropic receptors irrespective of whether the cells expressed the IL-2 rec eptor. IL-2-displaying vector particles could also transiently stimulate th e cell cycle entry and proliferation of several IL-2-dependent cell lines, Finally, retroviral vectors displaying IL-2 could efficiently transduce G0/ G1-arrested cells expressing the IL-2 receptor at a 34-fold higher efficien cy compared with vectors with unmodified envelopes. This new strategy, wher eby C-type retroviral vector particles display a ligand that activates the cell cycle of the target cells at the time of virus entry, may represent an alternative to lentivirus-derived retroviral vectors for the infection of quiescent cells. In addition, upon infection of an heterogeneous population of nonproliferating cells, MLV-retroviral vectors that display cytokines/g rowth factors will allow the transgene of interest to be integrated specifi cally in quiescent cells expressing the corresponding cytokine/growth facto r receptor (C) 1999 by The American Society of Hematology.