Characterization of selectivity of 2A2-ILP targeting to surface ROR1 on primary CLL cells. (A) The specific uptake of 2A2-ILP over control IgG-ILP by primary CLL was measure by intensity of fluorescence. (B) The in vivo selectivity of 2A2-ILP over IgG-ILP in organs from mice engrafted with hROR1 × TCL1 splenocytes. (C) The invasion of CD5⁺B220⁺ROR1⁺ leukemic cells (red) in BMMC of hROR1 × TCL1 mouse model. (D) The in vivo selectivity of 2A2-ILP over IgG-ILP recognizing ROR1⁺ leukemic cells in BMMC from mice engrafted with hROR1 × TCL1 splenocytes. (E) Treatment with miR-29b–encapsulated 2A2-ILP for 24 hours increased levels of intracellular miR-29b ∼600-fold over free form and sevenfold over isotype control IgG-ILP delivery in OSU-CLL cell line. (F29, free-form of miR-29b; SC, scrambled miR.) (F) Two-week treatment with 2A2-miR-29b-ILP significantly reduced the GDM of the CLL cell line by 58% compared with scramble in 2A2-ILP control. (G) Selective delivery of miR-29b decreases DNMTs and SP1 in OSU-CLL cell lines after 48 hours. Decitabine (Dec, 100 nM) was used as a positive control of hypomethylating agent.