Targeting cancer cells with nucleic acid aptamers

Cerchia, Laura; Franciscis, Vittorio de

doi:10.1016/j.tibtech.2010.07.005

Cited by 206 publications

(144 citation statements)

References 65 publications

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“…The whole SELEX process can be divided into several parts [8][9][10][11] (Fig.1). The starting point of the SELEX process is an establishment of a random DNA oligonucleotide library consisting of 10 12 -10 15 different sequences.…”

Section: Selex Processmentioning

confidence: 99%

Applications of Aptamers in Drug Delivery System

Wu¹

2017

WJPR

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Aptamers, a kind of short single-stranded oligonucleic acids (DNA or RNA) or peptide molecules that can fold into secondary or tertiary structures, are well recognized as a potential tool for binding target molecules due to its high specificity and affinity. As tumor targeted ligands, aptamers have certain superiorities compared with antibodies, such as low immunogenicity, high binding specificity and so on. By the means of systematic evolution of ligands with exponential enrichment (SELEX) approach, selected aptamers showed high affinity to specific targets like proteins, peptides, and even the entire cells. In this review, we will give a brief overview of recent relevant research in the field of aptamers and their applications in cancer diagnostics and in drug delivery system.

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Section: Selex Processmentioning

confidence: 99%

Applications of Aptamers in Drug Delivery System

Wu¹

2017

WJPR

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“…Table 2 lists additional aptamers that are in various phases of clinical development. Readers are referred to excellent recent reviews that provide a more in depth discussion of this new platform and its therapeutic potential (20)(21)(22)(23)(24).…”

Section: Oligonucleotide Aptamer Ligandsmentioning

confidence: 99%

Use of Oligonucleotide Aptamer Ligands to Modulate the Function of Immune Receptors

Gilboa

McNamara

Pastor

2013

Clinical Cancer Research

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The paucity of costimulation at the tumor site compromises the ability of tumor-specific T cells to eliminate the tumor. The recent U.S. Food and Drug Administration approval of ipilumimab, an antibody that blocks the inhibitory action of CTLA-4, and clinical trials targeting 4-1BB and PD-1 or PD-L1, have underscored the therapeutic potential of using immunomodulatory antibodies to stimulate protective immunity in human patients. Nonetheless, systemic administration of immunomodulatory antibodies has been associated with dose-limiting autoimmune pathologies, conceivably reflecting also the activation of resident autoreactive T cells. Arguably, targeting immunomodulatory ligands to the disseminated tumor lesions of the patient would reduce such drug-associated toxicities. We have recently developed a new class of inhibitory (CTLA-4) and agonistic (4-1BB and OX-40) ligands composed of short oligonucleotide (ODN) aptamers that exhibited bioactivities comparable or superior to that of antibodies. To reduce toxicity, the immunomodulatory aptamers were targeted to the tumor by conjugation to a second aptamer that bound to a product expressed on the surface of the tumor cell, the targeting aptamer, generating a bispecific aptamer conjugate analogous to bispecific antibodies. In a proof-of-concept study in mice, we have shown that an agonistic 4-1BB-binding aptamer conjugated to a prostate-specific membrane antigen (PSMA)-binding aptamer led to the inhibition of PSMA-expressing tumors, was more effective than, and synergized with, vaccination, and exhibited a superior therapeutic index compared with nontargeted costimulation with 4-1BB antibodies or 4-1BB aptamers. The cell-free chemically synthesized ODN aptamers offer significant advantages over antibodies in terms of synthesis, cost, as well as conjugation chemistry needed to generate bispecific ligand fusions.

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“…Aptamers have a number of distinct advantages over antibodies; they can be reliably duplicated in vitro in the precise volumes required, and, through the use of simple chemical modification, they can be protected from degradation by nucleases and have their lifespan in blood extended by up to 24 hours without major side effects. Aptamers can also be used as carriers of a wide range of medical drugs through their ability to be attached to various nanoparticles; aptamers which are sensitive to, for example, cancer markers on the surface of cancer cells can provide targeted delivery of chemotherapeutic or other drugs (Cerchia and de Franciscis 2010). The RNA aptamer Macugen, which was approved for clinical use in 2004, is very effective in the treatment of the devastating disease of age-related macular degeneration.…”

Section: Dna Aptamers In Medical Therapy and Drug Deliverymentioning

confidence: 99%

Potential uses of G-quadruplex-forming aptamers

Víglaský

Hianik

2013

gpb

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Abstract. Guanine quadruplex (G-quadruplex) structures are one of a number of structures which are capable of adopting aptamers. G-rich DNA or RNA has an increased propensity to form quadruplex structures which have unusual biophysical and biological properties. G-rich aptamers which form G-quadruplexes have several advantages over unstructured sequences: G-quadruplexes are non-immunogenic, thermodynamically and chemically stable and they have both higher resistance to various serum nucleases and an enhanced cellular uptake. These advantages have led to a number of synthetic oligonucleotides being studied for their potential use as therapeutic agents for cancer therapy and in the treatment of various other diseases. In addition to their suitability in the fields of medicine and biotechnology, these, highly specified, aptameric G-quadruplexes also have great potential in the further development of nano-devices; e.g. basic components in microarrays, microfluidics, sandwich assays and electrochemical biosensors. This review summarizes the biophysical properties of G-quadruplexes and highlights the importance of the stability and recognition properties of aptamers. Examples of the application of aptamers in medical therapy and in biosensors are also discussed.

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Targeting cancer cells with nucleic acid aptamers

Cited by 206 publications

References 65 publications

Applications of Aptamers in Drug Delivery System

Applications of Aptamers in Drug Delivery System

Use of Oligonucleotide Aptamer Ligands to Modulate the Function of Immune Receptors

Potential uses of G-quadruplex-forming aptamers

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