Aptamer-based targeted therapy

Abstract

Precision medicine holds great promise to harness genetic and epigenetic cues for targeted treatment of a variety of diseases, ranging from many types of cancers, neurodegenerative diseases, to cardiovascular diseases. The proteomic profiles resulting from the unique genetic and epigenetic signatures represent a class of relatively well accessible molecular targets for both interrogation (e.g., diagnosis, prognosis) and intervention (e.g., targeted therapy) of these diseases. Aptamers are promising for such applications by specific binding with cognate disease biomarkers. Nucleic acid aptamers are a class of DNA or RNA with unique three-dimensional conformations that allow them to specifically bind with target molecules. Aptamers can be relatively easily screened, reproducibly manufactured, programmably designed, and chemically modified for various biomedical applications, including targeted therapy. Aptamers can be chemically modified to resist enzymatic degradation or optimize their pharmacological behaviors, which ensured their chemical integrity and bioavailability under physiological conditions. In this review, we will focus on recent progress and discuss the challenges and opportunities in the research areas of aptamer-based targeted therapy in the forms of aptamer therapeutics and aptamer-drug conjugates (ApDCs).

Advancing Aptamers as Molecular Probes for Cancer Theranostic Applications—The Role of Molecular Dynamics Simulation

“…Chimeric ssDNA aptamer by cell-SELEX method Target CD 16 and c-MET overexpressed in tumors [184] Serum-stabilized ssDNA aptamer by hybrid-SELEX method CD30 cell membrane protein of tumor necrosis factor receptor family [185] Monothioate backbone-substituted X-aptamers CD44-hyaluronic acid binding domain (HABD) expressed in cancer stem cells [186] ssDNA monothiophosphate-modified aptamers CD44-HABD expressed in human ovarian cancer cells such as IGROV, SKOV3, and A2780 [187] Trimeric ErbB-2-specific ssDNA aptamers ErbB-2 expressed in human breast and N87 gastric cancer cells [188] Cell-SELEX selected ssDNA aptamers Human epidermal growth factor receptor 2 (HER2) overexpressed in human breast cancer (SK-BR-3) cell lines [189] ssDNA aptamer selected by protein-SELEX method Epithelial cell adhesion molecule (EpCAM) overexpressed by solid cancers [190] DNA aptamer selected by protein-SELEX method Fractalkine or CX 3 CL1 overexpressed by several cancer cells [191] TD05 DNA aptamer Membrane bound immunoglobin heavy mu chain in Burkitt's lymphoma cells (cancer of lymphatic system) [192] MA3 86-base DNA aptamer MUC1 (mucin-1) overexpressed in A549 lung and MCF-7 breast cancer cell lines [193] Phototoxic DNA aptamers MUC1 overexpressed in MCF-7, T47D human breast cancer, and PANC-1 human pancreatic cancer cell lines [194] 25 base long ssDNA aptamers MUC1 tumor marker [195] Dimeric DNA aptamer SZTI01 Prostate-specific membrane antigen overexpressed in human prostatic carcinoma (C4-2) cell lines [196] DNA aptamer selected by cell-SELEX method Protein tyrosine kinase 7 (PTK7) overexpressed in T-cell acute lymphoblastic leukemia cells [197] Chimeric DNA aptamer MUC1 in OVCAR-3 ovarian cancer cells [198] AS1411 aptamer Targets nucleolin and destabilizes Bcl-2 messenger RNA in human breast cancer cells [199,200] PDGF-B DNA aptamer Inhibition of platelet derived growth factor (PDGF) by binding with PDGF receptor and reducing tumor interstitial fluid [201] RCA aptamer immobilized in DNA network CD33 antigen in acute lymphoblastic leukemia [202] DNA aptamers Human carcinoembryonic antigen overexpressed on the surface of colorectal tumor cells [203] DNA aptamers CA15-3 overexpressed by breast cancer cell lines [204] DNA aptamers MUC1 peptide and Tn antigen in epithelial cancer cells [205] DNA aptamer-nanoparticle conjugation AS1411 and sgc8c polyvalent DNA aptamers-gold nanoparticles…”

<p>Aptamers as Versatile Ligands for Biomedical and Pharmaceutical Applications</p>

“…Previous investigators have presented reviews on aptamer discovery and applications. 11,12 However, these reports revolved around the synthesis of aptamers, aptamer-guided drug delivery, and targeted therapy. The biomedical and pharmaceutical applications of aptamers have not been fully reviewed.…”

Changes in Protein Glycosylation as a Result of Aptamer Interactions with Cancer Cells

“…[2] Aptamers interacting directly with cancer cells for cancer therapy can modulate the immune system and indirectly inhibit cancer cell growth. [2] Aptamers interacting directly with cancer cells for cancer therapy can modulate the immune system and indirectly inhibit cancer cell growth.…”

“…Therapeutic function of aptamers is of a great interest, as they can change the expression level of their target proteins. [2] Aptamers interacting directly with cancer cells for cancer therapy can modulate the immune system and indirectly inhibit cancer cell growth. [3] However, the mechanisms underlying the aptamer-mediated anti-proliferation effect have not been fully understood.…”