Application of aptamers for in vivo molecular imaging and theranostics

Bouvier-Müller, Alix; Ducongé, Frédéric

doi:10.1016/j.addr.2018.08.004

Cited by 76 publications

(52 citation statements)

References 108 publications

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“…Biodistribution and safety of E8. To determine the dispersion of E8 we used fluorescently-labeled E8 as previously described for aptamer in vivo imaging probes [30][31][32] . The molecule, modified with 5'-Cy5.5 and 3'-PEG, was injected intravenously in two doses (6 and 60 mg/kg) into NOD/SCID mice in which MDA-MB-231 tumors were induced.…”

Section: Resultsmentioning

confidence: 99%

Discovery of tumoricidal DNA oligonucleotides by response-directed in vitro evolution

et al. 2020

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Drug discovery is challenged by ineffectiveness of drugs against variable and evolving diseases, and adverse effects due to poor selectivity. We describe a robust platform which potentially addresses these limitations. The platform enables rapid discovery of DNA oligonucleotides evolved in vitro for exerting specific and selective biological responses in target cells. The process operates without a priori target knowledge (mutations, biomarkers, etc). We report the discovery of oligonucleotides with direct, selective cytotoxicity towards cell lines, as well as patient-derived solid and hematological tumors. A specific oligonucleotide termed E8, induced selective apoptosis in triple-negative breast cancer (TNBC) cells. Polyethylene glycol-modified E8 exhibited favorable biodistribution in animals, persisting in tumors up to 48-hours after injection. E8 inhibited tumors by 50% within 10 days of treatment in patient-derived xenograft mice, and was effective in ex vivo organ cultures from chemotherapy-resistant TNBC patients. These findings highlight a drug discovery model which is target-tailored and on-demand.

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Section: Resultsmentioning

confidence: 99%

Discovery of tumoricidal DNA oligonucleotides by response-directed in vitro evolution

et al. 2020

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“…To determine the dispersion of E8 we used fluorescently-labeled E8 as previously described for aptamer in-vivo imaging probes [30][31][32] . The molecule, modified with 5' Cy5.5 and 3' PEG, was injected intravenously in two doses (6 and 60 mg/kg) into NOD/SCID mice in which MDA-MB-231 tumors were induced.…”

Section: Resultsmentioning

confidence: 99%

Discovery of tumoricidal DNA oligonucleotides by effect-directedin-vitroevolution

Mamet

Amir

Lavi

et al. 2019

Preprint

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Our current model of drug discovery is challenged by the relative ineffectiveness of drugs against highly variable and rapidly evolving diseases and their relatively high incidence of adverse effects due to poor selectivity. Here we describe a robust and reproducible platform which could potentially address these limitations. The platform enables rapid, de-novo discovery of DNA aptamers evolved in-vitro to exert specific biological effects on target cells. Unlike conventional aptamers, which are selected by their ligand binding capacity, this platform is driven directly by therapeutic effect and selectivity towards target vs negative target cells. The process could, therefore, operate without any a-priori knowledge (e.g. mutations, biomarker expression, or known drug resistance) of the target. We report the discovery of DNA aptamers with direct and selective cytotoxicity towards several tumor cell lines as well as primary, patient-derived solid and hematological tumors, some with chemotherapy resistance. Aptamers discovered by this platform exhibited favorable biodistribution in animals, persistence in target tumors up to 48 hours after injection, and safety in human blood. These aptamers showed remarkable efficacy in-vivo as well as ex-vivo in freshly obtained, 3D cultured human tumors resistant to multiple chemotherapies. With further improvement, these findings could lead to a drug discovery model which is target-tailored, mechanism-flexible, and nearly on-demand.

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“…Recently, aptamers have also been proven as hopeful candidates of affinity molecules for target‐specific drug delivery . To date, many aptamers have been successfully selected against a variety of targets and applied on diverse fields . As compared with antibodies, aptamers are showing some unique advantages .…”

Section: Discussionmentioning

confidence: 99%

“…It has been widely used for screening of cancer cell‐specific aptamers as well as identification of novel biomarkers . To date, many target‐specific aptamers have been successfully selected and applied on diverse fields . For instance, Macugen is the first United States Food and Drug Administration‐approved aptamer drug for the treatment of age‐related macular degeneration .…”

Section: Introductionmentioning

confidence: 99%

Selection and characterization of novel DNA aptamer against colorectal carcinoma Caco‐2 cells

Maimaitiyiming

Yang

Wang

et al. 2019

Biotech and App Biochem

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Aptamers are short, single-stranded nucleic acid (DNA or RNA) oligonucleotides that can be obtained by a technique called systematic evolution of ligands by exponential enrichment (SELEX) in vitro. Due to superior properties such as small size, high binding affinity, and stability, they are considered to be feasible tools for diagnosis and treatment of disease. In the current study, we attempted to screen a high-affinity DNA aptamer to selectively target the colorectal carcinoma Caco-2 cells by using cell-based SELEX approach. After 14 consecutive rounds of selection, aptamer ApC1 was identified.Confocal microscopy results revealed that ApC1 could rapidly internalize into Caco-2 cells but not HEK 293 cells. Moreover, it showed high specificity to Caco-2 cells rather than other cell lines such as 293T, HeLa, MCF-7, HL-60, and NB4. Collectively, our results demonstrated that aptamer ApC1 has high specificity to colorectal carcinoma Caco-2 cells, which could be further applied for targeted therapy of colorectal cancer in future studies.Abbreviations: ssDNA, single-stranded DNA; SELEX, systematic evolution of ligands by exponential enrichment; ApDC, aptamer drug conjugate. .

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Application of aptamers for in vivo molecular imaging and theranostics

Cited by 76 publications

References 108 publications

Discovery of tumoricidal DNA oligonucleotides by response-directed in vitro evolution

Discovery of tumoricidal DNA oligonucleotides by response-directed in vitro evolution

Discovery of tumoricidal DNA oligonucleotides by effect-directedin-vitroevolution

Selection and characterization of novel DNA aptamer against colorectal carcinoma Caco‐2 cells

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