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a , Schematic diagram of ODC manufacturing and its mechanism of action. The ODC is generated <t>by</t> <t>conjugating</t> <t>DBCO-PEG4-VC-PAB-MMAE</t> with 5’ azide modified oligonucleotide via click chemistry. The resulting ODC selectively binds the csRNA target, enabling endocytosis-mediated internalization and subsequent lysosomal release of the drug payload. b , Electropherogram (left) and mass spectrum (right) of unconjugated and conjugated U1-targeted oligonucleotides obtained by capillary electrophoresis and LC-MS, respectively. The intensity in the mass spectrum was normalized to the maximum intensity. The standard lower marker (LM) and upper marker (UP) are shown. The purity is defined as the ratio of the product peak area to the total peak area. c , Representative immunofluorescence image of HeLa cells treated with U1-MMAE and stained with 9D5 (red) and MMAE antibody (green). The yellow arrows indicate the M-phase cell. The scale bars are 10µm. d , The intensity plot of the fluorescence channels across the green dashed line indicated in ( c ). e , Representative fluorescent images of HeLa cells under conditions treated with U1-MMAE, polyA-MMAE, random-MMAE or solvent (blank control), followed by fixation and DAPI staining. f , Quantification of cell counts per field of view under conditions shown in ( e ). One-way ANOVA, ****P < 0.0001. g , Cytotoxicity of U1-MMAE, scrambled U1-MMAE, polyA-MMAE and DBCO-MMAE in HeLa cells after a 72-h incubation. Error bars, standard deviation. n = 3. h , Volcano plot for differential analysis of csRNA levels between MDA-MB-231 and MCF-10A cell lines. Differentially detected csRNAs are identified using the Wilcoxon rank-sum test (p value < 0.05 and absolute value of log₂FC > 0.5), and the color of these csRNA dots represents the difference in percentage of cells expressing the csRNA. i , Cytotoxicity of SNORA70F-MMAE in MCF-10A and MDA-MB-231 cells after a 72-h incubation. Error bars, standard deviation. n = 3. j , Cytotoxicity of snoU2_19-MMAE in the ten CIRCmap-profiled cancer and non-tumorigenic cells after a 72-h incubation. Error bars, standard deviation. n = 3. k , Cytotoxicity of snoU2_19-MMAE in additional unprofiled cancer and non-tumorigenic cells after a 72-h incubation. Error bars, standard deviation. n = 2 for ARPE-19, n = 3 for other groups. l , Tumor growth curves in HeLa xenograft-bearing mice with intravenous administration of snoU2_19-MMAE, polyA-MMAE, scrambled snoU2_19-MMAE, and vehicle control. Error bars, standard error of the mean. n = 6, unpaired one-tail t-test (day 42), *P < 0.05, **P < 0.01. m , Body weight change in HeLa xenograft-bearing mice with intravenous administration of snoU2_19-MMAE, polyA-MMAE, scramble-MMAE, and vehicle control. Error bars, standard error of the mean. n = 6, unpaired one-tail t-test, ns, not significant.
Dbco Peg4 Vc Pab Mmae, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 94/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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a , Schematic diagram of ODC manufacturing and its mechanism of action. The ODC is generated by conjugating DBCO-PEG4-VC-PAB-MMAE with 5’ azide modified oligonucleotide via click chemistry. The resulting ODC selectively binds the csRNA target, enabling endocytosis-mediated internalization and subsequent lysosomal release of the drug payload. b , Electropherogram (left) and mass spectrum (right) of unconjugated and conjugated U1-targeted oligonucleotides obtained by capillary electrophoresis and LC-MS, respectively. The intensity in the mass spectrum was normalized to the maximum intensity. The standard lower marker (LM) and upper marker (UP) are shown. The purity is defined as the ratio of the product peak area to the total peak area. c , Representative immunofluorescence image of HeLa cells treated with U1-MMAE and stained with 9D5 (red) and MMAE antibody (green). The yellow arrows indicate the M-phase cell. The scale bars are 10µm. d , The intensity plot of the fluorescence channels across the green dashed line indicated in ( c ). e , Representative fluorescent images of HeLa cells under conditions treated with U1-MMAE, polyA-MMAE, random-MMAE or solvent (blank control), followed by fixation and DAPI staining. f , Quantification of cell counts per field of view under conditions shown in ( e ). One-way ANOVA, ****P < 0.0001. g , Cytotoxicity of U1-MMAE, scrambled U1-MMAE, polyA-MMAE and DBCO-MMAE in HeLa cells after a 72-h incubation. Error bars, standard deviation. n = 3. h , Volcano plot for differential analysis of csRNA levels between MDA-MB-231 and MCF-10A cell lines. Differentially detected csRNAs are identified using the Wilcoxon rank-sum test (p value < 0.05 and absolute value of log₂FC > 0.5), and the color of these csRNA dots represents the difference in percentage of cells expressing the csRNA. i , Cytotoxicity of SNORA70F-MMAE in MCF-10A and MDA-MB-231 cells after a 72-h incubation. Error bars, standard deviation. n = 3. j , Cytotoxicity of snoU2_19-MMAE in the ten CIRCmap-profiled cancer and non-tumorigenic cells after a 72-h incubation. Error bars, standard deviation. n = 3. k , Cytotoxicity of snoU2_19-MMAE in additional unprofiled cancer and non-tumorigenic cells after a 72-h incubation. Error bars, standard deviation. n = 2 for ARPE-19, n = 3 for other groups. l , Tumor growth curves in HeLa xenograft-bearing mice with intravenous administration of snoU2_19-MMAE, polyA-MMAE, scrambled snoU2_19-MMAE, and vehicle control. Error bars, standard error of the mean. n = 6, unpaired one-tail t-test (day 42), *P < 0.05, **P < 0.01. m , Body weight change in HeLa xenograft-bearing mice with intravenous administration of snoU2_19-MMAE, polyA-MMAE, scramble-MMAE, and vehicle control. Error bars, standard error of the mean. n = 6, unpaired one-tail t-test, ns, not significant.

Journal: bioRxiv

Article Title: Targeting cancer-associated cell surface RNAs with oligonucleotide-drug conjugates enables broad antitumor activity

doi: 10.64898/2026.05.08.723688

Figure Lengend Snippet: a , Schematic diagram of ODC manufacturing and its mechanism of action. The ODC is generated by conjugating DBCO-PEG4-VC-PAB-MMAE with 5’ azide modified oligonucleotide via click chemistry. The resulting ODC selectively binds the csRNA target, enabling endocytosis-mediated internalization and subsequent lysosomal release of the drug payload. b , Electropherogram (left) and mass spectrum (right) of unconjugated and conjugated U1-targeted oligonucleotides obtained by capillary electrophoresis and LC-MS, respectively. The intensity in the mass spectrum was normalized to the maximum intensity. The standard lower marker (LM) and upper marker (UP) are shown. The purity is defined as the ratio of the product peak area to the total peak area. c , Representative immunofluorescence image of HeLa cells treated with U1-MMAE and stained with 9D5 (red) and MMAE antibody (green). The yellow arrows indicate the M-phase cell. The scale bars are 10µm. d , The intensity plot of the fluorescence channels across the green dashed line indicated in ( c ). e , Representative fluorescent images of HeLa cells under conditions treated with U1-MMAE, polyA-MMAE, random-MMAE or solvent (blank control), followed by fixation and DAPI staining. f , Quantification of cell counts per field of view under conditions shown in ( e ). One-way ANOVA, ****P < 0.0001. g , Cytotoxicity of U1-MMAE, scrambled U1-MMAE, polyA-MMAE and DBCO-MMAE in HeLa cells after a 72-h incubation. Error bars, standard deviation. n = 3. h , Volcano plot for differential analysis of csRNA levels between MDA-MB-231 and MCF-10A cell lines. Differentially detected csRNAs are identified using the Wilcoxon rank-sum test (p value < 0.05 and absolute value of log₂FC > 0.5), and the color of these csRNA dots represents the difference in percentage of cells expressing the csRNA. i , Cytotoxicity of SNORA70F-MMAE in MCF-10A and MDA-MB-231 cells after a 72-h incubation. Error bars, standard deviation. n = 3. j , Cytotoxicity of snoU2_19-MMAE in the ten CIRCmap-profiled cancer and non-tumorigenic cells after a 72-h incubation. Error bars, standard deviation. n = 3. k , Cytotoxicity of snoU2_19-MMAE in additional unprofiled cancer and non-tumorigenic cells after a 72-h incubation. Error bars, standard deviation. n = 2 for ARPE-19, n = 3 for other groups. l , Tumor growth curves in HeLa xenograft-bearing mice with intravenous administration of snoU2_19-MMAE, polyA-MMAE, scrambled snoU2_19-MMAE, and vehicle control. Error bars, standard error of the mean. n = 6, unpaired one-tail t-test (day 42), *P < 0.05, **P < 0.01. m , Body weight change in HeLa xenograft-bearing mice with intravenous administration of snoU2_19-MMAE, polyA-MMAE, scramble-MMAE, and vehicle control. Error bars, standard error of the mean. n = 6, unpaired one-tail t-test, ns, not significant.

Article Snippet: DBCO-PEG4-VC-PAB-MMAE (MedChemExpress, HY-136314).

Techniques: Generated, Modification, Electrophoresis, Liquid Chromatography with Mass Spectroscopy, Marker, Immunofluorescence, Staining, Fluorescence, Solvent, Control, Incubation, Standard Deviation, Expressing