Combinatorial Selection of DNA Thioaptamers Targeted to the HA Binding Domain of Human CD44

Somasunderam, Anoma; Thiviyanathan, Varatharasa; Tanaka, Takemi; Li, Xin; Neerathilingam, Muniasamy; Lokesh, G.L.; Mann, Aman P.; Yang, Peng; Ferrari, Mauro; Klostergaard, Jim; Gorenstein, David G.

doi:10.1021/bi1009503

Cited by 91 publications

(62 citation statements)

References 48 publications

(72 reference statements)

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“…Somasunderam et al (2010) reported the selection of ssDNA thioaptamers that can bind hyaluronic acid binding domain of the CD44 receptor. The results of this study showed that the selected thioaptamers did bind the CD44 protein with a higher affinity (180-295 nM) compared with hyaluronic acid (K d > 61 mM).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Selection of Modified RNA Aptamers Against CD44 Cancer Stem Cell Marker

Ababneh

Alshaer

Allozi

et al. 2013

Nucleic Acid Therapeutics

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Cancer stem cells (CSCs) are a subset of tumor cells that has the ability to self-renew and to generate the diverse cells that comprise the tumor mass. The cell-surface glycoprotein CD44 is one of the most common surface markers used to identify CSCs. Aptamers are synthetic oligonucleotides selected from pools of random sequences that can bind to a wide range of targets with high affinity and specificity. In this study, the systematic evolution of ligands by exponential enrichment (SELEX) technology was used to isolate RNA aptamers using human recombinant full-length CD44 protein and 2'-F-pyrimidine modified RNA library with a complexity of around 10(14) different molecules. Following 11 iterative rounds of SELEX, the selected aptamers were cloned and sequenced. Three different sequences were identified. The binding specificities for one of these RNA aptamers was assessed using representative breast cancer cell lines expressing CD44; namely, MDA-MB-231, MCF7, and T47D. The selected RNA aptamer (Apt1) was found to interact specifically with such cancer cells when analyzed by flow cytometry and fluorescent microscopy, with different intensities of fluorescence reflecting the level of CD44 expression on the surface of these cells. It can be concluded that the selected aptamers can be used to target CD44 positive cells, including cancer stem cells, for detection, sorting, and enrichment and for drug delivery purposes.

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Section: Discussionmentioning

confidence: 99%

In Vitro Selection of Modified RNA Aptamers Against CD44 Cancer Stem Cell Marker

Ababneh

Alshaer

Allozi

et al. 2013

Nucleic Acid Therapeutics

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“…These aptamers bind specifically to CD44-expressing tumor cells with high efficacy. However, the in vivo bioavailability of these aptamers has not been examined in detail (Somasunderam et al, 2010). …”

Section: Targeting Ha Receptorsmentioning

confidence: 99%

Targeting Hyaluronic Acid Family for Cancer Chemoprevention and Therapy

Lokeshwar

Mirza

Jordan

2014

Advances in Cancer Research

135

113

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Hyaluronic acid or hyaluronan (HA) is perhaps one of the most uncomplicated large polymers that regulates several normal physiological processes and, at the same time, contributes to the manifestation of a variety of chronic and acute diseases, including cancer. Members of the HA signaling pathway (HA synthases, HA receptors, and HYAL-1 hyaluronidase) have been experimentally shown to promote tumor growth, metastasis, and angiogenesis, and hence each of them is a potential target for cancer therapy. Furthermore, as these members are also overexpressed in a variety of carcinomas, targeting of the HA family is clinically relevant. A variety of targeted approaches have been developed to target various HA family members, including small-molecule inhibitors and antibody and vaccine therapies. These treatment approaches inhibit HA-mediated intracellular signaling that promotes tumor cell proliferation, motility, and invasion, as well as induction of endothelial cell functions. Being nontoxic, nonimmunogenic, and versatile for modifications, HA has been used in nanoparticle preparations for the targeted delivery of chemotherapy drugs and other anticancer compounds to tumor cells through interaction with cell-surface HA receptors. This review discusses basic and clinical translational aspects of targeting each HA family member and respective treatment approaches that have been described in the literature.

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“…It is possible that for these cells that it binds to different peptide/proteins compared with the CCRF-CEM target cells, and the binding of these peptides/proteins affects cell growth. Some aptamers have been shown to bind to specific cell receptors and in one case thioaptamers were developed that bind the primary receptor for hyaluronic acid [37]. As this receptor plays an important function in tumour growth, it is possible that sgc8c may also bind similar receptors on the ovarian cancer cells, which may be the cause of their inherent cytotoxicity.…”

Section: Aptamer Effect On Phenen Cytotoxicity and Uptakementioning

confidence: 99%

DNA-based aptamer fails as a simultaneous cancer targeting agent and drug delivery vehicle for a phenanthroline-based platinum(II) complex

McGinely

Plumb

Wheate

2013

Journal of Inorganic Biochemistry

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The sgc8c aptamer is a 41-base DNA oligonucleotide that binds to leukaemia cells with high affinity and specificity. In this work we examined the utility of this aptamer as both a delivery vehicle and an active targeting agent for an inert platinum complex [(1,10-phenathroline)(ethylenediamine)platinum(II)] 2+ . The aptamer forms a stem-and-loop confirmation as determined by circular dichroism. This conformation is adopted in both water and phosphate buffered saline solutions. The metal complex binds to the aptamer through intercalation into the aptamer's double helical stem with a binding constant of approximately 4.3 × 10 4 M -1 . Binding of the metal complex to the aptamer had a significant effect on the aptamer's global conformation, and increased its melting temperature by 28 o C possibly through lengthening and stiffening of the aptamer stem. The effect of the aptamer on the metal complex's cytotoxicity and cellular uptake was determined using in vitro assays with the target leukaemia cell line CCRF-CEM and the off-target ovarian cancer cell lines A2780 and A2780cp70. The aptamer has little inherent cytotoxicity and when used to deliver the metal complex results in a significant decrease in the metal complex's cytotoxicity and uptake. The reason(s) for the poor uptake and activity may be due to the change in aptamer conformation which affects its ability to recognise leukaemia cells.

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Combinatorial Selection of DNA Thioaptamers Targeted to the HA Binding Domain of Human CD44

Cited by 91 publications

References 48 publications

In Vitro Selection of Modified RNA Aptamers Against CD44 Cancer Stem Cell Marker

In Vitro Selection of Modified RNA Aptamers Against CD44 Cancer Stem Cell Marker

Targeting Hyaluronic Acid Family for Cancer Chemoprevention and Therapy

DNA-based aptamer fails as a simultaneous cancer targeting agent and drug delivery vehicle for a phenanthroline-based platinum(II) complex

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