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. 2013 Jun 1;4(4):872-890.
doi: 10.4236/jct.2013.44099.

Nucleic Acid Aptamers as Potential Therapeutic and Diagnostic Agents for Lymphoma

Affiliations

Nucleic Acid Aptamers as Potential Therapeutic and Diagnostic Agents for Lymphoma

Ka-To Shum et al. J Cancer Ther. .

Abstract

Lymphomas are cancers that arise from white blood cells and usually present as solid tumors. Treatment of lymphoma often involves chemotherapy, and can also include radiotherapy and/or bone marrow transplantation. There is an un-questioned need for more effective therapies and diagnostic tool for lymphoma. Aptamers are single stranded DNA or RNA oligonucleotides whose three-dimensional structures are dictated by their sequences. The immense diversity in function and structure of nucleic acids enable numerous aptamers to be generated through an iterative in vitro selection technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Aptamers have several biochemical properties that make them attractive tools for use as potential diagnostic and pharmacologic agents. Isolated aptamers may directly inhibit the function of target proteins, or they can also be formulated for use as delivery agents for other therapeutic or imaging cargoes. More complex aptamer identification methods, using whole cancer cells (Cell-SELEX), may identify novel targets and aptamers to affect them. This review focuses on recent advances in the use of nucleic acid aptamers as diagnostic and therapeutic agents and as targeted delivery carriers that are relevant to lymphoma. Some representative examples are also discussed.

Keywords: Biosensor; Cell-Type Specific Drug Delivery; Lymphoma; Nanotechnology; Nucleic Acid Aptamer; SELEX.

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Figures

Figure 1
Figure 1
Cell-SELEX to identify aptamers that targets membrane proteins. First, a DNA library is transcribed and incubated with normal cells. Second, unbound nucleic acids are exposed to target cells that overexpress the membrane protein of interest for selection. Third, bound nucleic acids are recovered and amplified by PCR and subjected to further rounds of selection. This SELEX cycle is repeated 15 – 20 times to enrich for sequences that bind to the target cells.
Figure 2
Figure 2
A TD05 aptamer-nanoparticle strip biosensor for detecting a Burkitt’s lymphoma cell line (Ramos cells). A sample solution that contains Ramos cells is recognized by TD05 aptamer gold nanoparticles (TD05-Au-NP). The TD05 Au-NP-cell complexes are captured on the test zone by a second binding event between Ramos cells and immobilized Ramos cells that recognize aptamers (TE02). The accumulation of Au-NP results in a red band. The excess Au-NP continues to migrate and is captured on the control zone by a hybridization reaction between TD05-Au-NP and an oligonucleotide complementary to the TD05 aptamers, leading to a second red band. In the absence of Ramos cells, only the red band in the control zone is observed, showing that the assay is working properly.
Figure 3
Figure 3
An AS1411-miR-211 molecular beacon theranostic. AS-1411 aptamers on the nanoparticles escort the theranostic to nucleolin positive-cancer cells and promote internalization of the theranostic by binding with cell surface nucleolin proteins. Once internalized, the reducing cytoplasmic environment causes miR-221 molecular beacon to be separated from the nanoparticles. The miR-221 molecular beacon then hybridizes with cellular mature miR-221, leading to separation of the double-stranded molecular beacon and producing a strong fluorescent signal. Additionally, the binding of cellular miR-221 to miR-221 molecular beacon inhibits the functions of endogenous miR-221, reducing oncogene expression. In contrast, Cy 5.0 and BHQ2 fluorescence quencher in the miR-221 molecular bacon remain in close proximity in the absence of cellular miR-221.

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