Peer, DanZhu, PengchengCarman, ChristopherLieberman, JudyShimaoka, Motomu2019-10-052007Peer, D., P. Zhu, C. V. Carman, J. Lieberman, and M. Shimaoka. 2007. “Selective Gene Silencing in Activated Leukocytes by Targeting siRNAs to the Integrin Lymphocyte Function-Associated Antigen-1.” Proceedings of the National Academy of Sciences 104 (10): 4095–4100. https://doi.org/10.1073/pnas.0608491104.0027-84240744-28311091-6490http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483438Silencing gene expression by RNAi is a powerful method for exploring gene function and validating drug targets and potentially for therapy. Lymphocytes and other primary blood cells are resistant to lipid-based transfection in vitro and are difficult to target in vivo. We show here that antibody-protamine fusion proteins targeting the human integrin lymphocyte function-associated antigen-1 (LFA-1) efficiently deliver siRNAs and specifically induce silencing in primary lymphocytes, monocytes, and dendritic cells. Moreover, a fusion protein constructed from an antibody that preferentially recognizes activation-dependent conformational changes in LFA-1 selectively targets activated leukocytes and can be used to suppress gene expression and cell proliferation only in activated lymphocytes. The siRNA-fusion protein complexes do not cause lymphocyte activation or induce IFN responses. K562 cells expressing latent WT or constitutively activated LFA-1 engrafted in the lungs of SCID mice are selectively targeted by intravenously injected fusion protein-siRNA complexes, demonstrating the potential in vivo applicability of LFA-1-directed siRNA delivery.en-USJournal Article2019-10-0510.1073/pnas.0608491104