Aptamer–ODN Chimeras: Enabling Cell-Specific ODN Targeting Therapy
Abstract
1. Introduction
2. Aptamers
2.1. Introduction and Application
2.2. The Internalizing Capacity of Aptamers
2.3. Aptamers as Vehicles for Targeted Delivery of ODN
3. Aptamer–ODN Chimeras
3.1. Aptamer-siRNA Chimeras
3.2. Aptamer-ASO Chimeras
3.3. Aptamer-miRNA Chimeras
3.4. Aptamer-saRNA Chimeras
3.5. Aptamer-Decoy Chimeras
3.6. Aptamer-sgRNA Chimeras
3.7. Aptamer-CpG Chimeras
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
ODN | oligonucleotide |
siRNA | small interfering RNA |
saRNA | small activating RNA |
miRNA | microRNA |
sgRNA | single guide RNA |
shRNA | short hairpin RNA |
ASO | antisense oligonucleotide |
ApDCs | aptamer-drug conjugates |
AMO | Anti-miRNA ODN |
RNAi | RNA interference |
Ago 2 | Argonaute 2 |
RNase H | Ribonuclease H |
RIBOTAC | RNA-inducible ribonuclease-targeted chimera |
PROTAC | protein degradation-targeted chimera |
3′-UTR | 3′ Untranslated Region |
FDA | US Food and Drug Administration |
EMA | European Medicines Agency |
SELEX | systematic evolution of ligands by exponential enrichment |
WC-SELEX | whole cell SELEX |
FACS-WC-SELEX | fluorescence-activated cell sorting-assisted WC-SELEX |
MC-WC-SELEX | microfluidic chip system-assisted WC-SELEX |
3D-WC-SELEX | three-dimensional culture-assisted WC-SELEX |
NA-WC-SELEX | nanomaterial-assisted WC-SELEX |
RME | receptor-mediated endocytosis |
CME | clathrin-mediated endocytosis |
CvME | caveolae-mediated endocytosis |
DSB | double-stranded DNA break |
NHEJ | non-homologous end-joining |
HDR | homology-directed repair |
3WJ | the three-way junction motif |
pRNA | packaging RNA |
VEGF | vascular endothelial growth factor |
TfR | transferrin receptor |
PTK7 | protein tyrosine kinase 7 |
mCRPC | metastatic castration-resistant prostate cancer |
PSMA | prostate-specific membrane antigen |
Bcl-2 | B-cell lymphoma 2 |
Plk1 | polo-like kinase 1 |
DOX | doxorubicin |
SARS-CoV-2 | severe acute respiratory syndrome coronavirus 2 |
CEBPA | CCAAT/Enhancer Binding Protein Alpha |
PDAC | pancreatic ductal adenocarcinoma |
NF-κB | nuclear factor κB |
EGFR | epidermal growth factor receptor |
PD-L1 | programmed death-ligand 1 |
PD-1 | programmed cell death protein 1 |
RCA | rolled-loop amplification |
VSV-G | vesicular stomatitis virus G glycoprotein |
ABP | aptamer-binding protein |
AML | acute myeloid leukemia |
TLR9 | Toll-like receptor 9 |
DSPE | 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine |
HDL | high-density lipoprotein |
Apo-AI | Apolipoprotein AI |
SRBI | scavenger receptor class B type I |
NIR | near-infrared |
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ODNs | Aptamer’s Name/Target | Target | Disease | Year | Ref. |
---|---|---|---|---|---|
siRNA | A9/PMSA | laminA/C | prostate cancer | 2006 | [51] |
A10/PMSA | PLK1 and BCL2 | prostate cancer | 2006 | [36] | |
A10-3.2/PSMA | PLK1 | prostate cancer | 2009 | [52] | |
PSMA aptamers/PSMA | Smg-1/Upf-2 | colon cancer | 2010 | [53] | |
PSMA aptamers/PSMA | Smg-1/Upf-2 | prostate cancer | 2013 | [54] | |
A10-3/PSMA | DNA-PK | prostate cancer | 2015 | [55] | |
PSMA aptamers/PSMA | EGFR and survivin | prostate cancer | 2016 | [56] | |
A10-3.2/PSMA | MDM2 | prostate cancer | 2022 | [37] | |
A10-3.2/PSMA | CAT-1 | prostate cancer | 2022 | [57] | |
4-1BB aptamer/4-1BB | mTORC1 | antitumor immunity | 2014 | [58] | |
4-1BB aptamer/4-1BB | CD25 | antitumor immunity | 2017 | [59] | |
gp120 aptamer/gp120 glycoprotein | HIV-1 gag p17 | HIV | 2008 | [60] | |
gp120 aptamer/gp120 glycoprotein | HIV-1 tat/rev | HIV | 2009 | [61] | |
gp120 aptamer/gp120 glycoprotein | HIV-1 tat/rev | HIV | 2011 | [62] | |
gp120 aptamer/gp120 glycoprotein | HIV-1 tat/rev | HIV | 2011 | [63] | |
gp120 aptamer/gp120 glycoprotein | HIV-1 tat/rev | HIV | 2011 | [64] | |
gp120 aptamer/gp120 glycoprotein | HIV-1 tat/rev | HIV | 2013 | [65] | |
gp120 aptamer/gp120 glycoprotein | HIV-1 LTR | HIV | 2018 | [66] | |
CCR5 aptamer/CCR5 | TNPO3 | HIV | 2015 | [67] | |
CD4 aptamer/CD4 | HIV genes and/or CCR5 | HIV | 2011 | [68] | |
CD4 aptamer/CD4 | STAT5b | asthma | 2012 | [69] | |
CD4 aptamer/CD4 | HIV-PR | HIV | 2012 | [70] | |
CD4 aptamer/CD4 | CCR5 | HIV | 2013 | [71] | |
CD8AP17s/CD8 | GNLY | immune diseases | 2013 | [72] | |
BAFF-R aptamer/BAFF-R | STAT3 | non-Hodgkin’s lymphoma | 2013 | [73] | |
aptamer 32/U87-EGFRvIII | c-Met | gioma | 2014 | [74] | |
aptNCL/nucleolin | SLUG and NRP1 | lung cancer | 2014 | [75] | |
AS1411/nucleolin | Bcl-2 | breast cancer | 2018 | [76] | |
AS1411/nucleolin | OPN | gioma | 2022 | [42] | |
AS1411/nucleolin | SMG1 | antitumor immunity | 2022 | [77] | |
EpCAM aptamer/EpCAM | EpCAM | breast cancer/retinoblastoma | 2015 | [78] | |
EpCAM aptamer/EpCAM | survivin | breast cancer | 2015 | [79] | |
EpCAM aptamer/EpCAM | EpCAM | epithelial cancer | 2015 | [80] | |
EpCAM aptamer/EpCAM | PLK1 | breast cancer | 2015 | [81] | |
EpCAM aptamer/EpCAM | D5D | colon cancer | 2019 | [82] | |
EpCAM aptamer/EpCAM | PKCι | breast cancer | 2020 | [40] | |
EpCAM aptamer/EpCAM | D5D | lung cancer | 2020 | [83] | |
HER2 aptamer/HER2 | Bcl-2 | breast cancer | 2012 | [84] | |
HER2, HER3 aptamer/HER2, HER3 | EGFR | breast cancer | 2018 | [85] | |
HER2 aptamer/HER2 | EGFR | breast cancer | 2018 | [86] | |
HER2 aptamer/HER2 | XBP1 | breast cancer | 2020 | [41] | |
EGFR aptamer/EGFR | Bcl-2 and PKC-ι | breast cancer | 2019 | [87] | |
EGFR aptamer/EGFR | XBP1 | breast cancer | 2021 | [39] | |
EGFR aptamer/EGFR | KRAS | non-small cell lung cancer | 2023 | [88] | |
ErbB3 aptamer/ErbB3 | survivin | breast cancer | 2020 | [89] | |
sgc8c and sgc4f/PTK7 | VEGF | leukemia | 2016 | [90] | |
mucin-1 aptamers/mucin-1 (MUC1) | BCL2 | multidrug-resistant breast cancer | 2017 | [91] | |
VEGF aptamer/VEGF | notch 3 | ovarian cancer | 2017 | [92] | |
GBN/RGNNV coat protein (CP) protein | viral CP | viral nervous necrosis | 2020 | [93] | |
LYGV1c/coat protein (CP) protein | SGIV MCP and VP19 | grouper iridovirus infection | 2021 | [94] | |
CTLA4 aptamer/CTLA4 | STAT3 | colorectal cancer | 2014 | [95] | |
αvβ3 aptamer/αvβ3 | EEF2 | prostate cancer/cervical cancer/glioblastoma | 2013 | [96] | |
Gint4.T/PDGFRβ | STAT3 | glioblastoma | 2018 | [97] | |
Gint4.T/PDGFRβ | STAT3 | glioblastoma | 2020 | [98] | |
Gint4.T/PDGFRβ | STAT3 | non-small cell lung cancer | 2023 | [99] | |
FB4/TfR | ICAM-1 | neuroinflammatory disease | 2014 | [100] | |
IGFIIR aptamer/IGFIIR | PCBP2 | antifibrotic | 2017 | [101] | |
monocytes/macrophages aptamer/monocytes/macrophages | ADK | immune diseases | 2018 | [102] | |
shRNA | CD40 aptamer/CD40 | SMG1 | B lymphoma and bone-marrow aplasia | 2015 | [103] |
CD40 aptamer/CD40 | RORγt | immune diseases | 2014 | [104] | |
CD30 aptamer/CD30 | RORγt | autoimmune inflammatory diseases | 2019 | [105] | |
S3R3/integrase | HIV-1 tat/rev | HIV | 2018 | [106] | |
A10/PSMA | DNAPK | prostate cancer | 2011 | [107] |
ODNs | Aptamer’s Name/Target | Target | Disease | Year | Ref. |
---|---|---|---|---|---|
ASO | AS1411/nucleolin | luciferase | pancreatic cancer | 2012 | [132] |
TfR aptamer/TfR | caspase-3 | ischemic stroke | 2013 | [133] | |
S6 aptamer/A549 | MMP-9 | lung cancer | 2015 | [134] | |
AS1411/nucleolin | galectin-1 | breast cancer | 2016 | [135] | |
Apt-2/LAMP1 | MALAT1 | lung cancer | 2021 | [28] | |
AS1411/nucleolin | c-myc | lung cancer | 2021 | [136] | |
PA9-1/PD-L1 | PD-L1 | antitumor immunity | 2023 | [137] | |
SApt/SARS-CoV-2 spike protein | SARS-CoV-2 nucleocapsid | SARS-CoV-2 | 2023 | [138] |
ODNs | Aptamer’s Name/Target | Target | Disease | Year | Ref. |
---|---|---|---|---|---|
miRNA | CD133 aptamer/CD133 | Anti-miR21 | triple-negative breast cancer | 2019 | [117] |
EGFR aptamer/EGFR | Anti-miR21 | breast cancer | 2015 | [116] | |
EGFR aptamer/EGFR | Anti-miR21 | breast cancer | 2021 | [154] | |
A549 aptamer/A549 | miR-301b-3p | lung adenocarcinoma | 2023 | [118] | |
α9-nAChR aptamer/α9-nAChR | Anti-miR21 | breast cancer | 2023 | [115] | |
MUC1 aptamer/MUC1 | PTEN | ovarian cancer | 2013 | [155] | |
GL21.T/Axl | HMGA2 | non-small cell lung cancer | 2014 | [153] | |
GL21.T/Axl | miR-222 | glioblastoma | 2015 | [147] | |
GL21.T and Gint4.T/PDGFRβ and Axl | miR-137 and anti-miR-10b | glioblastoma | 2016 | [151] | |
GL21.T/Axl | PED/PEA-15 | non-small cell lung cancer | 2016 | [152] | |
GL21.T/Axl | AXL | non-small cell lung cancer | 2018 | [150] | |
GL21.T/Axl | Axl and the miR-137 | non-small cell lung cancer | 2019 | [156] | |
AS1411/nucleolin | c-raf-1 | non-small cell lung cancer | 2018 | [157] | |
AS1411/nucleolin | miRNA let-7d | gastric cancer | 2019 | [149] | |
A10–3.2/PSMA | Bcl-2, cyclin D1, Wnt3a | prostate cancer | 2011 | [158] | |
cKIT aptamer/cKIT | Ezh2 and Bak1 | breast cancer | 2023 | [159] | |
apt69.T/B cell maturation antigen | miR-137 and miR-122 | multiple myeloma | 2019 | [146] |
ODNs | Aptamer’s Name/Target | Target | Disease | Year | Ref. |
---|---|---|---|---|---|
saRNA | P19/P1 aptamer/PDAC | C/EBPα | pancreatic cancer | 2016 | [167] |
TR14/hTfR | C/EBPα | prostate cancer | 2019 | [168] | |
A10-3.2/PSMA | DPYSL3 | prostate cancer | 2016 | [169] | |
m12-3773/clusterin and 1-717/TMED6 | XIAP | prostate cancer | 2022 | [170] | |
decoy | c2.min/hTfR | NF-κB | pancreatic cancer | 2015 | [171] |
GS-24/TfR | NF-κB | cerebrovascular inflammation | 2015 | [172] |
ODNs | Aptamer’s Name/Target | Target | Disease | Year | Ref. |
---|---|---|---|---|---|
cpg | IL-4Rα/IL-4Rα receptor | CpG-induced pathways | antitumor immunity | 2017 | [196] |
AS1411/nucleolin | CpG-induced pathways | antitumor immunity | 2018 | [181] | |
AS1411/nucleolin | CpG-induced pathways | antitumor immunity | 2024 | [197] | |
Aapt/ATP | CpG-induced pathways | antitumor immunity | 2021 | [198] | |
ROX40 aptamer/ROX40 | CpG-induced pathways | antitumor immunity | 2025 | [199] | |
MUC1 aptamer/MUC1 | CpG-induced pathways | antitumor immunity | 2019 | [200] | |
PD-L1 aptamer/PD-L1 | CpG-induced pathways | metastatic lung cancer | 2023 | [201] | |
PD-L1 aptamer/PD-L1 | CpG-induced pathways | antitumor immunity | 2022 | [202] | |
PD-L1 aptamer/PD-L1 | CpG-induced pathways | post-operative tumor recurrence | 2023 | [182] | |
others | com/Com | sgRNA | duchenne muscular dystrophy | 2021 | [179] |
PD-1 aptamer/PD-1 | sgRNA | antitumor immunity | 2019 | [190] | |
SS30/CD123 | sgRNA | acute myeloid leukemia | 2019 | [180] | |
NCL-APT/nucleolin | survivin | retinoblastoma | 2021 | [203] | |
MUC1 aptamer/MUC1 | Egr-1 | breast cancer | 2020 | [204] | |
Sgc8/PTK7 | MET | lung cancer | 2020 | [205] | |
CD44-EpCAM aptamer/CD44 and EpCAM | CD44 and EpCAM | ovarian cancer | 2017 | [206] | |
TfR-aptamer/TfR | Tau | tauopathy | 2020 | [207] |
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Xia, B.; Zhu, Q. Aptamer–ODN Chimeras: Enabling Cell-Specific ODN Targeting Therapy. Cells 2025, 14, 697. https://doi.org/10.3390/cells14100697
Xia B, Zhu Q. Aptamer–ODN Chimeras: Enabling Cell-Specific ODN Targeting Therapy. Cells. 2025; 14(10):697. https://doi.org/10.3390/cells14100697
Chicago/Turabian StyleXia, Bei, and Qubo Zhu. 2025. "Aptamer–ODN Chimeras: Enabling Cell-Specific ODN Targeting Therapy" Cells 14, no. 10: 697. https://doi.org/10.3390/cells14100697
APA StyleXia, B., & Zhu, Q. (2025). Aptamer–ODN Chimeras: Enabling Cell-Specific ODN Targeting Therapy. Cells, 14(10), 697. https://doi.org/10.3390/cells14100697