American Association for Cancer Research
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FIGURE 3 from Nanoparticle Delivery of Immunostimulatory Alu RNA for Cancer Immunotherapy

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posted on 2023-09-08, 14:20 authored by Kyle M. Garland, Alexander J. Kwiatkowski, John T. Tossberg, Philip S. Crooke, Thomas M. Aune, John T. Wilson

In vitro characterization of AluJb RNA (Left Arm)/D-PDB. A, Agarose gel of AluJb RNA (Left Arm) with and without various amounts of D-PDB, as indicated. 1 µg RNA/lane. The TrackIt 100 bp DNA Ladder was employed. B, DLS analysis of Alu-NPs and Edited Alu-NPs (i.e., AluJb RNA (Left Arm)/D-PDB at an N/P ratio of 4 and Inactive AluJB (Left Arm)/D-PDB at an N/P ratio of 4) relative to D-PDB. C, TEM images of D-PDB NPs, Edited Alu-NPs, and Alu-NPs. Scale bars, 100 µm. RAW-Dual (D) and THP1-Dual (E) reporter cell assays of Alu-NPs, Edited Alu-NPs, D-PDB, D-B Alu NPs, and Free AluJB RNA (Left Arm). All curves are normalized to the maximum value of the Alu-NPs. All experiments were performed at least twice.


National Science Foundation (NSF)

DOD | USA | MEDCOM | Congressionally Directed Medical Research Programs (CDMRP)

American Cancer Society (ACS)

HHS | National Institutes of Health (NIH)



Loss of A-to-I editing leads to accumulation of unedited Alu RNAs that activate innate immunity via RNA-sensing pattern recognition receptors. When packaged into endosome-releasing polymer nanoparticles, AluJB RNA becomes highly immunostimulatory and can be used pharmacologically to inhibit tumor growth in mouse melanoma models. These findings identify Alu RNAs as a new class of nucleic acid innate immune agonists for cancer immunotherapy.